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研究生:鄒瑞煌
研究生(外文):Ruey-Hwang Chou
論文名稱:亞砷酸鈉在含人類乳突病毒E6及E7致癌基因之人類癌細胞的細胞毒性機制研究
論文名稱(外文):The Cytotoxic Effects of Sodium Arsenite in Human Papillomaviruses E6 and E7 Oncogenes -Containing Human Cancer Cells
指導教授:黃海美
指導教授(外文):Haimei Huang
學位類別:博士
校院名稱:國立清華大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:106
中文關鍵詞:亞砷酸鈉人類乳突病毒E6蛋白質p53蛋白質E7蛋白質Rb蛋白質程序性凋亡蛋白質激活酵素A
外文關鍵詞:sodium arsenitehuman papillomavirusesE6p53E7Rbapoptosisprotein kinase A
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  • 收藏至我的研究室書目清單書目收藏:2
砷化合物是常見的天然產生物。研究顯示,砷化合物是人類的致癌物質,和肺癌、膀胱癌、皮膚癌、肝癌、腎臟癌及前列腺癌的產生有關。然而,砷化物被用在治療上已有超過2400年的歷史,最近三氧化二砷被廣泛用於治療急性前骨髓淋巴癌(APL),美國食品及藥物管理局(FDA)已於西元2000年9月核准三氧化二砷為急性前骨髓淋巴癌的合法用藥。
子宮頸癌高居婦女癌症死亡原因的第二位。超過百分之九十的子宮頸癌細胞被不同型的人類乳突病毒(HPV)感染,而這些細胞大多擁有正常的p53和Rb兩種抑癌基因。但是,在這些子宮頸癌細胞裡,正常的p53及Rb功能分別被人類乳突病毒的E6及E7致癌基因所抑制,因此,藉由破壞p53/E6或是Rb/E7間的作用途徑是蠻有潛力的治療子宮頸癌策略。這篇論文主要是研究亞砷酸鈉對人類乳突病毒E6和E7致癌基因的影響,亞砷酸鈉對於細胞程序性凋亡(Apoptosis)的影響,並研究亞砷酸鈉毒殺人類乳突病毒感染的子宮頸癌細胞的可能機制。
人類的類淋巴母細胞(TK6)和它的E6轉殖細胞(TK6-E6)以及原本就被16型HPV感染的人類子宮頸癌細胞(SiHa)是本實驗所使用的兩個系統。在人類的類淋巴母細胞方面,亞砷酸鈉能減少TK6-E6細胞的E6致癌基因轉錄,並誘導p53抑癌蛋白和它下游的p21及MDM2蛋白質的表現,然而X-射線則無此作用。與TK6細胞相較,亞砷酸鈉會增加TK6-E6細胞程序性凋亡的反應,包括產生較多的sub-G1比例、較多活化態的caspase-3(17 kD)以及較多的DNA ladder。根據MTT分析的結果得知:與TK6細胞相較,TK6-E6細胞對亞砷酸鈉較為敏感,但對X-射線則較不敏感。這意味著將來在治療有E6感染的癌細胞時,亞砷酸鈉也許可取代游離輻射而達到較好治療效果。
在人類子宮頸癌細胞方面,亞砷酸鈉會抑制HPV E6及E7致癌基因的轉錄,恢復正常p53抑癌基因的功能並誘導Rb蛋白質的表現。在亞砷酸鈉恢復p53基因功能的同時,也伴隨著細胞週期停滯在G2/M期以及細胞程序性凋亡現象的產生。轉殖dominant-negative p53基因至子宮頸癌細胞中,以抑制亞砷酸鈉所誘導正常p53的功能,顯箸地減少細胞程序性凋亡現象。這結果顯示亞砷酸鈉會藉由活化p53居間的途徑而造成子宮頸癌細胞的程序性凋亡。
除了p53之外,還有一些會被HPV E6蛋白分解的分子,例如:Bak和Myc,參與細胞程序性凋亡的調控。據研究指出,Bak蛋白質會被E6蛋白質的C端結合。蛋白質激活酵素A(cAMP-dependent protein kinase A 或PKA)能藉由磷酸化E6蛋白質C端區域上的第156個threonine而抑制它的功能,而此區域不參與E6蛋白質結合和分解p53蛋白質。在本論文中,我主要是研究PKA在調控亞砷酸鈉所誘導的程序性凋亡中所扮演的角色。前處理PKA的抑制劑(HA1004)顯著地減少亞砷酸鈉對SiHa細胞和TK6-E6細胞(皆有E6基因)所造成的細胞程序性凋亡現象,但是HA1004對於TK6細胞(沒有E6基因)則無此作用。這意味著PKA在調控E6蛋白質參與亞砷酸鈉所誘導的程序性凋亡上扮演著重要角色。此外,只有在SiHa細胞和TK6-E6細胞(皆有E6基因)前處理HA1004可以減少亞砷酸鈉所誘導的Bak蛋白質表現,而在TK6細胞(沒有E6基因)則無此現象。然而,在前述的三種細胞中,HA1004對於亞砷酸鈉所誘導的p53蛋白質均無作用。這些結果顯示:在含有E6的癌細胞中,PKA能抑制E6蛋白質去分解亞砷酸鈉所誘導的Bak蛋白質的能力,進而影響細胞程序性凋亡現象,而PKA並不能抑制E6蛋白質去分解亞砷酸鈉所誘導的p53蛋白質的功能。
根據以上的研究結果,亞砷酸鈉在含有HPV的癌細胞中會誘導細胞程序性凋亡現象可能的原因為:(1)抑制E6和E7兩致癌基因表現,(2)恢復癌細胞的p53抑癌基因功能,以及(3)有部分是PKA參與抑制E6蛋白質去分解Bak蛋白質的能力。

Arsenic compounds are common, naturally occurring substances. They have been reported to be human carcinogens associated with malignancies of the lung, bladder, skin, liver, kidney, and prostate. However, arsenic compounds have been used as therapeutic agents for more than 2,400 years. Recently, arsenic trioxide (As2O3) was wildly used to cure acute promyelocytic leukemia (APL). The Food and Drug Administration (FDA) of the USA has approved arsenic trioxide for the treatment of APL in September 2000.
Cervical cancer is the second leading cause of death from cancer in women worldwide. Over 90% of human cervical cancer cells are infected with different types of human papillomaviruses (HPVs) and possess wild type p53 and Rb tumor suppressor genes. But in these cells, normal p53 and Rb functions are abolished by HPVs E6 and E7 oncogenes, respectively. Therefore, restoration of p53 or Rb function by blocking E6/p53 or E7/Rb pathway might be a potential therapeutic purpose for these cancer cells. In the present study, we investigated the effects of sodium arsenite (SA) on HPVs E6 and E7 oncogenes, the effects of SA on apoptotic responses, and try to promote SA as a potential therapeutic agent for HPV-positive cancer cells.
Two systems were used in this study: (1) the human lymphoblastoid cells (TK6 cells), and their E6-transfectants (TK6-E6 cells), (2) the human cervical carcinoma cells originally infected with HPV-16 (SiHa cells). Treatment with SA, but not X-ray, decreased the E6 mRNA levels and induced the expressions of p53, and its down stream genes, p21, and mdm2 in TK6-E6 cells. SA enhanced apoptotic responses, including more sub-G1 percentages, more activated caspase-3 fragments (17 kD), and more DNA ladder in TK6-E6 cells than these in their parental TK6 cells. According to the results from MTT assay, TK6-E6 cells were more sensitive to SA, but more resistant to ionizing radiation (IR) than TK6 cells. It implied that instead of IR, SA could be a potential therapeutic agent for E6-possitive cancer cells.
In human cervical cancer cells, SA down-regulated E6 and E7 mRNA levels, restored p53 tumor suppressor pathway, and induced Rb expression. While SA restored normal p53 function, G2/M arrest in the cell cycle progression and apoptosis occurred. Transfection of a dominant-negative p53 markedly reduced the SA-induced apoptosis, indicating that p53 mediated SA-induced apoptosis in SiHa cells.
Besides p53, other molecules are involved in regulation of apoptosis. Cyclic AMP-dependent protein kinase A (PKA) has been reported to inhibit E6 function by phosphorylation of threonine residue at its C-terminal region, which is not involved in p53 binding and degradation. But, E6 binds to Bak, an apoptosis inducer, at this region. In this study, I investigated the roles of PKA in regulation of SA-induced apoptosis. Pretreatment with a PKA inhibitor, HA1004, significantly reduced the SA-induced apoptotic cell death in E6-positive SiHa and TK6-E6 cells, but not in E6-negative TK6 cells. It implied that PKA played some roles in regulation of E6 function, which was involved in SA-induced apoptosis, in E6-positive cancer cells. Furthermore, pretreatment with HA1004 decreased SA-induced Bak expression only in E6-possitive cancer cells. However, HA1004 did not affect SA-induced p53 expression in both E6-positive and E6-negative cancer cells. These results suggested that PKA inhibited E6 degrading SA-induced Bak, and resulted in apoptotic cell death in E6-positive cancer cells, but PKA could not inhibit the E6 function of degradation of SA-induced p53.
Base on these above results, SA-induced apoptotic cell death in HPV-positive cancer cells might result from the following: (1) down regulation of E6 and E7 oncogenes, (2) restoration of the p53 tumor suppressor pathway, and (3) at least in part, involvement of PKA in inhibition of Bak degradation by E6.

Contents
Contents …………………………………………………………….………… 1
Publication List and Conferences …………………………………………... 5
Abbreviations ………………………………………………….……………... 6
中文摘要 ……………………………………………………………………..… 7
Abstract ……………………………………………………………………..… 9
Chapter 1
Background
1.1 Arsenic Compounds ...……………………………………………... 11
1.2 The Possible Modes of Action of Arsenic Carcinogenesis …...….… 11
1.3 Arsenic compounds in Therapy ……………………………………. 15
1.4 Possible Mechanisms of Action of Arsenic Trioxide (As2O3) in Cancer Treatment ……………………………………………….……..….... 16
1.5 Human Papillomaviruses (HPVs) ……………………………….… 18
1.6 The HPVs E6 oncoproteins ……………………………………...… 18
1.7 The HPVs E7 oncoproteins ………………………………………... 26
1.8 Cyclic-AMP Dependent Protein Kinase (PKA) ………..……………. 26
1.9 Specific Aims ……………………………………………………..... 28
Chapter 2
Sodium Arsenite Suppresses Human Papillomavirus-16 E6 Gene and Enhances Apoptosis in E6-Transfected Human Lymphoblastoid Cells
2.1 Abstract …………………………………………………………….. 29
2.2 Introduction ………………………………………………………… 30
2.3 Materials and Methods
Materials ……………………………………………………...…….. 32
Cells and Culture Conditions ……………………………………….. 32
Transfection of HPV16-E6 Gene ……………………………………... 32
Western Blotting …………………………………………………….. 33
Genomic DNA Extraction and Polymerase Chain Reaction (PCR) .... 33
RNA Extraction and Reverse Transcription Polymerase Chain Reaction (RT-PCR) …………………………………………………….………. 34
DNA Analysis by Flow Cytometry …………………………….…….. 35
DNA Fragmentation Assay ……………………………………….….. 35
MTT Assay ……………………………………………………….…... 35
2.4 Results
Selection of Neo and E6 Transfected Clones ………………….……... 37
HPV16 E6 mRNA Levels were Down Regulated by SA ………….... 37
SA Altered p53, p21waf1/cip1 and MDM2 Protein Levels ………………... 37
SA Enhanced Apoptotic Responses in E6-Transfected TK6 Cells .….. 38
E6-Transfected TK6 Cells were More Sensitive to SA, but More Resistant to IR ………………….……………………………………….…...…… 39
2.5 Discussion
The Possible Reasons Why TK6-E6 Cells Were More Sensitive to SA than TK6 Cells …………………………………………………………….… 40
The Possible Reasons Why p53 Proteins Were Induced by SA in E6-Transfected TK6 Cells …………… ……………………………… 40
Potential Therapeutic Roles of Arsenite in HPV-positive Cancer Cells ….. 41
Conclusions ………………………………………………………………. 42
2.6 Tables ……………….. …………………………………………………… 43
2.7 Figures . …………………………………………………………………... 44
Chapter 3
Restoration of p53 Tumor Suppressor Pathway in Human Cervical Carcinoma Cells by Sodium Arsenite
3.1 Abstract …………………………………. ………………………………. 50
3.2 Introduction ………………………………………………………… …… 51
3.3 Materials and Methods
Materials …………….…….. ……………………………………………. 53
Cells and Culture Conditions …………………………… ………………. 53
RNA Extraction and Reverse Transcription Polymerase Chain Reaction (RT-PCR) …………. …………………………………………………… 53
Western Blotting ………………………………………………………... 54
Immuno-Fluorescence Staining of Cellular p53 ……………………….. 54
Flow Cytometric Analysis ……………………………………………… 54
Dual-Parameter Flow Cytometric Analysis of Normal, Apoptotic, and Necrotic Cells ………………………………………………………… 54
Apoptotic Cells Staining ……….. ……………………………………….. 54
DNA Fragmentation Assay …………………………………………….. 55
Plasmid Construction and Transfection ………………………………….. 55
3.4 Results
HPV-16 E6 mRNA Levels Were Down-Regulated by SA, but not by IR
…………………………………………………………………………. 56
SA Activated The p53 Tumor Suppressor Pathway and Caused p53 Accumulation in Cellular Nuclei ……………………………………….. 56
SA Suppressed HPV-16 E7 Oncogene and Induced Rb Expression …… 56
SA Blocked The Cell Cycle Progression in G2/M Phase Coinciding with Decreased Cdc25A and Cyclins ………………………………………... 57
Induction of Apoptosis Was The Major Event after SA Treatment … …… 57
Expression of Dominant-Negative p53 Significantly Rescued SiHa Cells from SA-Induced Apoptotic Cell Death ………………………………... 58
3.5 Discussion ……………………………………………………………. 59
Other Similar Researches ………………………………………………... 59
The Possible Reasons Why p53 Function Was Restored by SA in SiHa Cells
…………………………………………………………………………... 59
The Possible Reasons Why SA Induced G2/M Arrest in SiHa Cells .. …...60
The Possible Reasons Why SA Induced Apoptotic Responses in SiHa Cells
………………………… ……………………………………………….. 60
Conclusions ………………………………. ……………………………... 61
3.6 Tables …………………………………………………………………….. 62
3.7 Figures …………………………………………………………….……. 65
Chapter 4
Involvement of cAMP-Dependent Protein Kinase (PKA) in Arsenite-Induced Apoptosis in E6-Positive Cancer Cells
4.1 Abstract …………. …………………………………………………….. 70
4.2 Introduction ……………………… ……………………………………. 71
4.3 Materials and Methods
Materials ………………………………………………………………... 73
Cells and Culture Conditions ………………………………………… 73
Dual-Parameter Flow Cytometric Analysis of Normal, Apoptotic, and Necrotic Cells ………………………………………………………… 73
Western Blotting …………………………………………………….. 73
4.4 Results
PKA Inhibitor, HA 1004, Protected E6-Positive Cancer Cells from SA-Induced Apoptotic Cell Death. …………………………………….. 74
HA1004 Reduced SA-Induced Bak Expression, but Had No Effect on SA-Induced p53 Expression in E6-Positive Cancer Cells. ………………. 74
4.5 Discussion
PKA and Apoptosis …………………………………………………... 76
The Possible Relationship Among E6, Bak, and Apoptosis ……………. 76
Conclusions …………………………………………………………… 77
4.6 Figures ……………………………….. ………………….………...… 78
Chapter 5
Conclusions and Perspectives
5.1 Conclusions …………………………………...………...…………… 81
5.2 Perspectives ……………………………………………...…………... 82
5.3 References …………………………………...………………………. 83

Abdulkarim B, Sabri S, Deutsch E, Chagraoui H, Maggiorella L, Thierry J, Eschwege F, Vainchenker W, Chouaib S, Bourhis J (2002): Antiviral agent Cidofovir restores p53 function and enhances the radiosensitivity in HPV-associated cancers. Oncogene 21:2334-46.
Abernathy CO, Liu YP, Longfellow D, Aposhian HV, Beck B, Fowler B, Goyer R, Menzer R, Rossman T, Thompson C, Waalkes M (1999): Arsenic: health effects, mechanisms of actions, and research issues. Environ Health Perspect 107:593-7.
Agarwal ML, Agarwal A, Taylor WR, Stark GR (1995): p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci U S A 92:8493-7.
Antman KH (2001): Introduction: the history of arsenic trioxide in cancer therapy. Oncologist 6:1-2.
Arnold LL, Cano M, St John M, Eldan M, van Gemert M, Cohen SM (1999): Effects of dietary dimethylarsinic acid on the urine and urothelium of rats. Carcinogenesis 20:2171-9.
Aronson SM (1994): Arsenic and old myths. R I Med 77:233-4.
Aurelio ON, Kong XT, Gupta S, Stanbridge EJ (2000): p53 mutants have selective dominant-negative effects on apoptosis but not growth arrest in human cancer cell lines. Mol Cell Biol 20:770-8.
Band V, De Caprio JA, Delmolino L, Kulesa V, Sager R (1991): Loss of p53 protein in human papillomavirus type 16 E6-immortalized human mammary epithelial cells. J Virol 65:6671-6.
Banks L, Edmonds C, Vousden KH (1990): Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells. Oncogene 5:1383-9.
Basu A, Mahata J, Gupta S, Giri AK (2001): Genetic toxicology of a paradoxical human carcinogen, arsenic: a review. Mutat Res 488:171-94.
Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG (2001): Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10:687-92.
Berg JM (1986): Potential metal-binding domains in nucleic acid binding proteins. Science 232:485-7.
Bilder D, Li M, Perrimon N (2000): Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289:113-6.
Bouwes Bavinck JN, Berkhout RJ (1997): HPV infections and immunosuppression. Clin Dermatol 15:427-37.
Boyer SN, Wazer DE, Band V (1996): E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Cancer Res 56:4620-4.
Brown J, Higo H, McKalip A, Herman B (1997): Human papillomavirus (HPV) 16 E6 sensitizes cells to atractyloside- induced apoptosis: role of p53, ICE-like proteases and the mitochondrial permeability transition. J Cell Biochem 66:245-55.
Brown JL, Kitchin KT (1996): Arsenite, but not cadmium, induces ornithine decarboxylase and heme oxygenase activity in rat liver: relevance to arsenic carcinogenesis. Cancer Lett 98:227-31.
Chellappan S, Kraus VB, Kroger B, Munger K, Howley PM, Phelps WC, Nevins JR (1992): Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci U S A 89:4549-53.
Chen CJ, Chen CW, Wu MM, Kuo TL (1992): Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. Br J Cancer 66:888-92.
Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM, Liu MM, He KL, Niu C, Ma J, Zhang P, Zhang TD, Paul P, Naoe T, Kitamura K, Miller W, Waxman S, Wang ZY, de The H, Chen SJ, Chen Z (1997a): Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood 89:3345-53.
Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z (1996): In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88:1052-61.
Chen JJ, Hong Y, Androphy EJ (1997b): Mutational analysis of transcriptional activation by the bovine papillomavirus type 1 E6. Virology 236:30-6.
Chen JJ, Reid CE, Band V, Androphy EJ (1995): Interaction of papillomavirus E6 oncoproteins with a putative calcium-binding protein. Science 269:529-31.
Chen TC, Hinton DR, Zidovetzki R, Hofman FM (1998a): Up-regulation of the cAMP/PKA pathway inhibits proliferation, induces differentiation, and leads to apoptosis in malignant gliomas. Lab Invest 78:165-74.
Chen YC, Lin-Shiau SY, Lin JK (1998b): Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J Cell Physiol 177:324-33.
Choi KS, Eom YW, Kang Y, Ha MJ, Rhee H, Yoon JW, Kim SJ (1999): Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells. J Biol Chem 274:31775-83.
Chou RH, Huang H (2002a): Restoration of p53 tumor suppressor pathway in human cervical carcinoma cells by sodium arsenite. Biochem Biophys Res Commun 293:298-306.
Chou RH, Huang H (2002b): Sodium arsenite suppresses human papillomavirus-16 E6 gene and enhances apoptosis in E6-transfected human lymphoblastoid cells. J Cell Biochem 84:615-24.
Cohen GM (1997): Caspases: the executioners of apoptosis. Biochem J 326 ( Pt 1):1-16.
Cohen MH, Hirschfeld S, Flamm Honig S, Ibrahim A, Johnson JR, O'Leary JJ, White RM, Williams GA, Pazdur R (2001): Drug approval summaries: arsenic trioxide, tamoxifen citrate, anastrazole, paclitaxel, bexarotene. Oncologist 6:4-11.
Cordon-Cardo C (1995): Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol 147:545-60.
Crompton M (2000): Mitochondrial intermembrane junctional complexes and their role in cell death. J Physiol 529 Pt 1:11-21.
Crook T, Tidy JA, Vousden KH (1991a): Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell 67:547-56.
Crook T, Wrede D, Vousden KH (1991b): p53 point mutation in HPV negative human cervical carcinoma cell lines. Oncogene 6:873-5.
Cutler EG, Bradford EH (1878): Action of iron, cod-liver oil, and arsenic on the globular richness of the blood. Am J Med Sci 75:74-84.
Cuzick J, Sasieni P, Evans S (1992): Ingested arsenic, keratoses, and bladder cancer. Am J Epidemiol 136:417-21.
Dai J, Weinberg RS, Waxman S, Jing Y (1999): Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system. Blood 93:268-77.
Dalal S, Gao Q, Androphy EJ, Band V (1996): Mutational analysis of human papillomavirus type 16 E6 demonstrates that p53 degradation is necessary for immortalization of mammary epithelial cells. J Virol 70:683-8.
de Villiers EM (1997): Papillomavirus and HPV typing. Clin Dermatol 15:199-206.
Debbas M, White E (1993): Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev 7:546-54.
Degenhardt YY, Silverstein SJ (2001): Gps2, a protein partner for human papillomavirus E6 proteins. J Virol 75:151-60.
Delnomdedieu M, Basti MM, Otvos JD, Thomas DJ (1993): Transfer of arsenite from glutathione to dithiols: a model of interaction. Chem Res Toxicol 6:598-602.
Denk C, Butz K, Schneider A, Durst M, Hoppe-Seyler F (2001): p53 mutations are rare events in recurrent cervical cancer. J Mol Med 79:283-288.
Desaintes C, Hallez S, Van Alphen P, Burny A (1992): Transcriptional activation of several heterologous promoters by the E6 protein of human papillomavirus type 16. J Virol 66:325-33.
Dey A, Atcha IA, Bagchi S (1997): HPV16 E6 oncoprotein stimulates the transforming growth factor-beta 1 promoter in fibroblasts through a specific GC-rich sequence. Virology 228:190-9.
Doskeland SO, Maronde E, Gjertsen BT (1993): The genetic subtypes of cAMP-dependent protein kinase--functionally different or redundant? Biochim Biophys Acta 1178:249-58.
Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R (1996): Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85:1067-76.
Dreau D, Culberson C, Wyatt S, Holder WD, Jr. (2000): Human papilloma virus in melanoma biopsy specimens and its relation to melanoma progression. Ann Surg 231:664-71.
Du YH, Ho PC (2001): Arsenic compounds induce cytotoxicity and apoptosis in cisplatin- sensitive and -resistant gynecological cancer cell lines. Cancer Chemother Pharmacol 47:481-90.
Duan J, Macey DJ, Pareek PN, Brezovich IA (2001): Real-time monitoring and verification of in vivo high dose rate brachytherapy using a pinhole camera. Med Phys 28:167-73.
Duensing S, Duensing A, Crum CP, Munger K (2001): Human papillomavirus type 16 E7 oncoprotein-induced abnormal centrosome synthesis is an early event in the evolving malignant phenotype. Cancer Res 61:2356-60.
Dyson N (1998): The regulation of E2F by pRB-family proteins. Genes Dev 12:2245-62.
Dyson N, Howley PM, Munger K, Harlow E (1989): The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243:934-7.
Edmonds C, Vousden KH (1989): A point mutational analysis of human papillomavirus type 16 E7 protein. J Virol 63:2650-6.
Elbel M, Carl S, Spaderna S, Iftner T (1997): A comparative analysis of the interactions of the E6 proteins from cutaneous and genital papillomaviruses with p53 and E6AP in correlation to their transforming potential. Virology 239:132-49.
El-Mahdy MA, Hamada FM, Wani MA, Zhu Q, Wani AA (2000): p53-degradation by HPV-16 E6 preferentially affects the removal of cyclobutane pyrimidine dimers from non-transcribed strand and sensitizes mammary epithelial cells to UV-irradiation. Mutat Res 459:135-45.
Etscheid BG, Foster SA, Galloway DA (1994): The E6 protein of human papillomavirus type 16 functions as a transcriptional repressor in a mechanism independent of the tumor suppressor protein, p53. Virology 205:583-5.
Evans RM, Hollenberg SM (1988): Zinc fingers: gilt by association. Cell 52:1-3.
Fan S, Smith ML, Rivet DJ, 2nd, Duba D, Zhan Q, Kohn KW, Fornace AJ, Jr., O'Connor PM (1995): Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Cancer Res 55:1649-54.
Findik D, Song Q, Hidaka H, Lavin M (1995): Protein kinase A inhibitors enhance radiation-induced apoptosis. J Cell Biochem 57:12-21.
Foster SA, Demers GW, Etscheid BG, Galloway DA (1994): The ability of human papillomavirus E6 proteins to target p53 for degradation in vivo correlates with their ability to abrogate actinomycin D-induced growth arrest. J Virol 68:5698-705.
Gallardo D, Drazan KE, McBride WH (1996): Adenovirus-based transfer of wild-type p53 gene increases ovarian tumor radiosensitivity. Cancer Res 56:4891-3.
Gao Q, Srinivasan S, Boyer SN, Wazer DE, Band V (1999): The E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation. Mol Cell Biol 19:733-44.
Gardiol D, Kuhne C, Glaunsinger B, Lee SS, Javier R, Banks L (1999): Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 18:5487-96.
Germolec DR, Spalding J, Boorman GA, Wilmer JL, Yoshida T, Simeonova PP, Bruccoleri A, Kayama F, Gaido K, Tennant R, Burleson F, Dong W, Lang RW, Luster MI (1997): Arsenic can mediate skin neoplasia by chronic stimulation of keratinocyte-derived growth factors. Mutat Res 386:209-18.
Germolec DR, Spalding J, Yu HS, Chen GS, Simeonova PP, Humble MC, Bruccoleri A, Boorman GA, Foley JF, Yoshida T, Luster MI (1998): Arsenic enhancement of skin neoplasia by chronic stimulation of growth factors. Am J Pathol 153:1775-85.
Germolec DR, Yoshida T, Gaido K, Wilmer JL, Simeonova PP, Kayama F, Burleson F, Dong W, Lange RW, Luster MI (1996): Arsenic induces overexpression of growth factors in human keratinocytes. Toxicol Appl Pharmacol 141:308-18.
Gerstner G, Kucera H, Weghaupt K, Rotter M (1986): [Does radiosterilization of the vagina occur through therapeutic radiation dosages?]. Strahlenther Onkol 162:693-7.
Giaccia AJ, Kastan MB (1998): The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 12:2973-83.
Goodwin EC, DiMaio D (2000): Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways [In Process Citation]. Proc Natl Acad Sci U S A 97:12513-8.
Gorby MS (1988): Arsenic poisoning. West J Med 149:308-15.
Greider CW, Blackburn EH (1985): Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405-13.
Greskovich JF, Jr., Macklis RM (2000): Radiation therapy in pregnancy: risk calculation and risk minimization. Semin Oncol 27:633-45.
Gross-Mesilaty S, Reinstein E, Bercovich B, Tobias KE, Schwartz AL, Kahana C, Ciechanover A (1998): Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway. Proc Natl Acad Sci U S A 95:8058-63.
Gulliver GA, Herber RL, Liem A, Lambert PF (1997): Both conserved region 1 (CR1) and CR2 of the human papillomavirus type 16 E7 oncogene are required for induction of epidermal hyperplasia and tumor formation in transgenic mice. J Virol 71:5905-14.
Gurr JR, Liu F, Lynn S, Jan KY (1998): Calcium-dependent nitric oxide production is involved in arsenite-induced micronuclei. Mutat Res 416:137-48.
Haas-Kogan DA, Kogan SC, Levi D, Dazin P, T'Ang A, Fung YK, Israel MA (1995): Inhibition of apoptosis by the retinoblastoma gene product. Embo J 14:461-72.
Habuchi T, Kinoshita H, Yamada H, Kakehi Y, Ogawa O, Wu WJ, Takahashi R, Sugiyama T, Yoshida O (1994): Oncogene amplification in urothelial cancers with p53 gene mutation or MDM2 amplification. J Natl Cancer Inst 86:1331-5.
Haller JS (1975): Therapeutic mule: the use of arsenic in the nineteenth century materia medica. Pharm Hist 17:87-100.
Hamadeh HK, Vargas M, Lee E, Menzel DB (1999): Arsenic disrupts cellular levels of p53 and mdm2: a potential mechanism of carcinogenesis. Biochem Biophys Res Commun 263:446-9.
Hanahan D, Weinberg RA (2000): The hallmarks of cancer. Cell 100:57-70.
Harbour JW, Dean DC (2000): Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2:E65-7.
Harley CB, Futcher AB, Greider CW (1990): Telomeres shorten during ageing of human fibroblasts. Nature 345:458-60.
Haupt Y, Rowan S, Oren M (1995): p53-mediated apoptosis in HeLa cells can be overcome by excess pRB. Oncogene 10:1563-71.
Hawkins DS, Demers GW, Galloway DA (1996): Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. Cancer Res 56:892-8.
Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT (1989): HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. Embo J 8:3905-10.
Hayashi H, Kanisawa M, Yamanaka K, Ito T, Udaka N, Ohji H, Okudela K, Okada S, Kitamura H (1998): Dimethylarsinic acid, a main metabolite of inorganic arsenics, has tumorigenicity and progression effects in the pulmonary tumors of A/J mice. Cancer Lett 125:83-8.
Helou K, Walentinsson A, Kost-Alimova M, Levan G (2001): Hgfr/Met oncogene acts as target for gene amplification in DMBA-induced rat sarcomas: free chromatin fluorescence in situ hybridization analysis of amplicon arrays in homogeneously staining regions. Genes Chromosomes Cancer 30:416-20.
Hengstermann A, Linares LK, Ciechanover A, Whitaker NJ, Scheffner M (2001): Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells. Proc Natl Acad Sci U S A 98:1218-23.
Hietanen S, Lain S, Krausz E, Blattner C, Lane DP (2000): Activation of p53 in cervical carcinoma cells by small molecules. Proc Natl Acad Sci U S A 97:8501-6.
Hostynek JJ, Hinz RS, Lorence CR, Price M, Guy RH (1993): Metals and the skin. Crit Rev Toxicol 23:171-235.
Huang H, Huang CF, Wu DR, Jinn CM, Jan KY (1993a): Glutathione as a cellular defence against arsenite toxicity in cultured Chinese hamster ovary cells. Toxicology 79:195-204.
Huang H, Huang CF, Wu DR, Jinn CM, Jan KY (1993b): Glutathione as a cellular defence against arsenite toxicity in cultured Chinese hamster ovary cells. Toxicology 79:195-204.
Huang H, Li CY, Little JB (1996): Abrogation of P53 function by transfection of HPV16 E6 gene does not enhance resistance of human tumour cells to ionizing radiation. Int J Radiat Biol 70:151-60.
Huang XJ, Wiernik PH, Klein RS, Gallagher RE (1999): Arsenic trioxide induces apoptosis of myeloid leukemia cells by activation of caspases. Med Oncol 16:58-64.
Hudson JB, Bedell MA, McCance DJ, Laiminis LA (1990): Immortalization and altered differentiation of human keratinocytes in vitro by the E6 and E7 open reading frames of human papillomavirus type 18. J Virol 64:519-26.
Huibregtse JM, Scheffner M, Howley PM (1991): A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. Embo J 10:4129-35.
IARC (1987): IARC monographs on the evaluation of the carcinogenic risk of chemicals to man. Supplement 7.: "Arsenic and arsenic compounds." IARC, Lyon, France.
Innocente SA, Abrahamson JL, Cogswell JP, Lee JM (1999): p53 regulates a G2 checkpoint through cyclin B1. Proc Natl Acad Sci U S A 96:2147-52.
Ip SM, Huang TG, Yeung WS, Ngan HY (2001): pRb-expressing adenovirus Ad5-Rb attenuates the p53-induced apoptosis in cervical cancer cell lines. Eur J Cancer 37:2475-83.
Ito C, Kusano E, Akimoto T, Takeda S, Sasaki N, Umino T, Iimura O, Ando Y, Asano Y (2002): Cilostazol enhances IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway. Cell Signal 14:625-32.
Jackson S, Harwood C, Thomas M, Banks L, Storey A (2000): Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Genes Dev 14:3065-73.
Jewers RJ, Hildebrandt P, Ludlow JW, Kell B, McCance DJ (1992): Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocytes. J Virol 66:1329-35.
Jiang XH, Chun-Yu Wong B, Yuen ST, Jiang SH, Cho CH, Lai KC, Lin MC, Kung HF, Lam SK (2001): Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3. Int J Cancer 91:173-179.
Jing Y, Dai J, Chalmers-Redman RM, Tatton WG, Waxman S (1999): Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood 94:2102-11.
Joho KE, Darby MK, Crawford ET, Brown DD (1990): A finger protein structurally similar to TFIIIA that binds exclusively to 5S RNA in Xenopus. Cell 61:293-300.
Jun CD, Pae HO, Yoo JC, Kwak HJ, Park RK, Chung HT (1998): Cyclic adenosine monophosphate inhibits nitric oxide-induced apoptosis in human leukemic HL-60 cells. Cell Immunol 183:13-21.
Kakizuka A, Miller WH, Jr., Umesono K, Warrell RP, Jr., Frankel SR, Murty VV, Dmitrovsky E, Evans RM (1991): Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 66:663-74.
Kapahi P, Takahashi T, Natoli G, Adams SR, Chen Y, Tsien RY, Karin M (2000): Inhibition of NF-kappa B activation by arsenite through reaction with a critical cysteine in the activation loop of Ikappa B kinase. J Biol Chem 275:36062-6.
Katakura K, Chang KP (1989): H DNA amplification in Leishmania resistant to both arsenite and methotrexate. Mol Biochem Parasitol 34:189-91.
Kessis TD, Slebos RJ, Nelson WG, Kastan MB, Plunkett BS, Han SM, Lorincz AT, Hedrick L, Cho KR (1993): Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proc Natl Acad Sci U S A 90:3988-92.
Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ (1995): Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 374:736-9.
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994): Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011-5.
Kinoshita T, Shirasawa H, Shino Y, Moriya H, Desbarats L, Eilers M, Simizu B (1997): Transactivation of prothymosin alpha and c-myc promoters by human papillomavirus type 16 E6 protein. Virology 232:53-61.
Kitasato H, Hillova J, Lenormand M, Hill M (1991): Tumorigenicity of the E6 and E6-E7 gene constructions derived from human papillomavirus type 33. Anticancer Res 11:1165-72.
Kitchin KT (2001): Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol Appl Pharmacol 172:249-61.
Kiyono T, Hiraiwa A, Fujita M, Hayashi Y, Akiyama T, Ishibashi M (1997): Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94:11612-6.
Klaassen CD (1996): Heavy metals and heavy-metal antagonists. In Hardman JG, Gilman AG, Limbird LE (eds): "Goodman and Gilman's The Pharmacological Basis of Therapeutics." New York: McGraw-Hill, pp 1649-1672.
Klingelhutz AJ, Foster SA, McDougall JK (1996): Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380:79-82.
Kondo S, Barnett GH, Hara H, Morimura T, Takeuchi J (1995): MDM2 protein confers the resistance of a human glioblastoma cell line to cisplatin-induced apoptosis. Oncogene 10:2001-6.
Kroemer G, de The H (1999): Arsenic trioxide, a novel mitochondriotoxic anticancer agent? J Natl Cancer Inst 91:743-5.
Kuhne C, Banks L (1998): E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box. J Biol Chem 273:34302-9.
Kuhne C, Gardiol D, Guarnaccia C, Amenitsch H, Banks L (2000): Differential regulation of human papillomavirus E6 by protein kinase A: conditional degradation of human discs large protein by oncogenic E6. Oncogene 19:5884-91.
Kuo ML, Kunugi KA, Lindstrom MJ, Kinsella TJ (1997): The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma cells. Cancer J Sci Am 3:163-73.
Kwong YL, Todd D (1997): Delicious poison: arsenic trioxide for the treatment of leukemia. Blood 89:3487-8.
Lechner MS, Laimins LA (1994): Inhibition of p53 DNA binding by human papillomavirus E6 proteins. J Virol 68:4262-73.
Lee D, Lee B, Kim J, Kim DW, Choe J (2000a): cAMP response element-binding protein-binding protein binds to human papillomavirus E2 protein and activates E2-dependent transcription. J Biol Chem 275:7045-51.
Lee JO, Russo AA, Pavletich NP (1998): Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature 391:859-65.
Lee SS, Glaunsinger B, Mantovani F, Banks L, Javier RT (2000b): Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. J Virol 74:9680-93.
Lee SS, Weiss RS, Javier RT (1997): Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A 94:6670-5.
Lee TC, Tanaka N, Lamb PW, Gilmer TM, Barrett JC (1988): Induction of gene amplification by arsenic. Science 241:79-81.
Lee-Chen SF, Wang MC, Yu CT, Wu DR, Jan KY (1993): Nickel chloride inhibits the DNA repair of UV-treated but not methyl methanesulfonate-treated Chinese hamster ovary cells. Biol Trace Elem Res 37:39-50.
Lees RE, Steele R, Wardle D (1985): Arsenic, syphilis, and cancer of the prostate. J Epidemiol Community Health 39:227-30.
Lertbutsayanukul C, Lertsanguansinchai P, Shotelersuk K, Khorprasert C, Rojpornpradit P, Asavametha N, Pataramontree J, Suriyapee S, Tresukosol D, Termrungruanglert W (2001): Results of radiation therapy in stage 1B cervical carcinoma at King Chulalongkorn Memorial Hospital: fifteen-year experience. J Med Assoc Thai 84 Suppl 1:S216-27.
Lew YS, Brown SL, Griffin RJ, Song CW, Kim JH (1999): Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown. Cancer Res 59:6033-7.
Li JH, Rossman TG (1989): Mechanism of comutagenesis of sodium arsenite with n-methyl-n-nitrosourea. Biol Trace Elem Res 21:373-81.
Li X, Coffino P (1996): High-risk human papillomavirus E6 protein has two distinct binding sites within p53, of which only one determines degradation. J Virol 70:4509-16.
Li YM, Broome JD (1999): Arsenic targets tubulins to induce apoptosis in myeloid leukemia cells. Cancer Res 59:776-80.
Liu Y, McKalip A, Herman B (2000): Human papillomavirus type 16 E6 and HPV-16 E6/E7 sensitize human keratinocytes to apoptosis induced by chemotherapeutic agents: Roles of p53 and caspase activation. J Cell Biochem 78:334-349.
Macleod KF, Hu Y, Jacks T (1996): Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system. Embo J 15:6178-88.
Maeda H, Hori S, Nishitoh H, Ichijo H, Ogawa O, Kakehi Y, Kakizuka A (2001): Tumor growth inhibition by arsenic trioxide (As2O3) in the orthotopic metastasis model of androgen-independent prostate cancer. Cancer Res 61:5432-40.
Mahieux R, Pise-Masison C, Gessain A, Brady JN, Olivier R, Perret E, Misteli T, Nicot C (2001): Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1- and type 2-infected cells by a caspase-3-dependent mechanism involving Bcl-2 cleavage. Blood 98:3762-9.
Malachowski ME (1990): An update on arsenic. Clin Lab Med 10:459-72.
Mantovani F, Banks L (1999): Inhibition of E6 induced degradation of p53 is not sufficient for stabilization of p53 protein in cervical tumour derived cell lines. Oncogene 18:3309-15.
Mantovani F, Banks L (2001): The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20:7874-87.
Marcello A, Massimi P, Banks L, Giacca M (2000): Adeno-associated virus type 2 rep protein inhibits human papillomavirus type 16 E2 recruitment of the transcriptional coactivator p300. J Virol 74:9090-8.
Mass MJ, Wang L (1997): Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis. Mutat Res 386:263-77.
Matsui M, Nishigori C, Toyokuni S, Takada J, Akaboshi M, Ishikawa M, Imamura S, Miyachi Y (1999): The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease. J Invest Dermatol 113:26-31.
McCabe MJ, Jr., Singh KP, Reddy SA, Chelladurai B, Pounds JG, Reiners JJ, Jr., States JC (2000): Sensitivity of myelomonocytic leukemia cells to arsenite-induced cell cycle disruption, apoptosis, and enhanced differentiation is dependent on the inter-relationship between arsenic concentration, duration of treatment, and cell cycle phase [In Process Citation]. J Pharmacol Exp Ther 295:724-33.
McCance DJ, Kopan R, Fuchs E, Laimins LA (1988): Human papillomavirus type 16 alters human epithelial cell differentiation in vitro. Proc Natl Acad Sci U S A 85:7169-73.
Melnick A, Licht JD (1999): Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 93:3167-215.
Mietz JA, Unger T, Huibregtse JM, Howley PM (1992): The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. Embo J 11:5013-20.
Moolgavkar SH (1986): Carcinogenesis modeling: from molecular biology to epidemiology. Annu Rev Public Health 7:151-69.
Moreno S, Nurse P, Russell P (1990): Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast. Nature 344:549-52.
Morosov A, Phelps WC, Raychaudhuri P (1994): Activation of the c-fos gene by the HPV16 oncoproteins depends upon the cAMP-response element at -60. J Biol Chem 269:18434-40.
Munger K, Scheffner M, Huibregtse JM, Howley PM (1992): Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer Surv 12:197-217.
Munshi NC (2001): Arsenic trioxide: an emerging therapy for multiple myeloma. Oncologist 6:17-21.
Murgo AJ (2001): Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the national cancer institute cooperative research and development studies. Oncologist 6:22-8.
Myklebust JH, Josefsen D, Blomhoff HK, Levy FO, Naderi S, Reed JC, Smeland EB (1999): Activation of the cAMP signaling pathway increases apoptosis in human B-precursor cells and is associated with downregulation of Mcl-1 expression. J Cell Physiol 180:71-80.
Nagata S (1997): Apoptosis by death factor. Cell 88:355-65.
Nakagawa S, Huibregtse JM (2000): Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol 20:8244-53.
Ned R, Allen S, Vande Pol S (1997): Transformation by bovine papillomavirus type 1 E6 is independent of transcriptional activation by E6. J Virol 71:4866-70.
Nevins JR (1998): Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ 9:585-93.
Nordenson I, Beckman G, Beckman L, Nordstrom S (1978): Occupational and environmental risks in and around a smelter in northern Sweden. II. Chromosomal aberrations in workers exposed to arsenic. Hereditas 88:47-50.
Nordenson I, Beckman L (1991): Is the genotoxic effect of arsenic mediated by oxygen free radicals? Hum Hered 41:71-3.
Orlov SN, Thorin-Trescases N, Dulin NO, Dam TV, Fortuno MA, Tremblay J, Hamet P (1999): Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3. Cell Death Differ 6:661-72.
Ouellette M, Borst P (1991): Drug resistance and P-glycoprotein gene amplification in the protozoan parasite Leishmania. Res Microbiol 142:737-46.
Palitti F, Cortes F, Bassi L, Di Chiara D, Fiore M, Pinero J (1993): Higher G2 sensitivity to the induction of chromosomal damage in the CHO mutant EM9 than in its parental line AA8 by camptothecin, an inhibitor of DNA topoisomerase I. Mutat Res 285:281-5.
Park JW, Choi YJ, Jang MA, Baek SH, Lim JH, Passaniti T, Kwon TK (2001): Arsenic trioxide induces g2/m growth arrest and apoptosis after caspase-3 activation and bcl-2 phosphorylation in promonocytic u937 cells. Biochem Biophys Res Commun 286:726-34.
Park WH, Seol JG, Kim ES, Hyun JM, Jung CW, Lee CC, Kim BK, Lee YY (2000): Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res 60:3065-71.
Parvathenani LK, Buescher ES, Chacon-Cruz E, Beebe SJ (1998): Type I cAMP-dependent protein kinase delays apoptosis in human neutrophils at a site upstream of caspase-3. J Biol Chem 273:6736-43.
Patel D, Huang SM, Baglia LA, McCance DJ (1999): The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. Embo J 18:5061-72.
Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ (2000): AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins. J Virol 74:5872-9.
Pim D, Massimi P, Banks L (1997): Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53 and suppresses transformed cell growth. Oncogene 15:257-64.
Poddar S, Mukherjee P, Talukder G, Sharma A (2000): Dietary protection by iron against clastogenic effects of short-term exposure to arsenic in mice in vivo. Food Chem Toxicol 38:735-7.
Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, Cordon-Cardo C, DePinho RA (1998): The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92:713-23.
Pott WA, Benjamin SA, Yang RS (2001): Pharmacokinetics, metabolism, and carcinogenicity of arsenic. Rev Environ Contam Toxicol 169:165-214.
Praetorius F (1997): HPV-associated diseases of oral mucosa. Clin Dermatol 15:399-413.
Puthenveettil JA, Frederickson SM, Reznikoff CA (1996): Apoptosis in human papillomavirus16 E7-, but not E6-immortalized human uroepithelial cells. Oncogene 13:1123-31.
Raimondi S (1972): [Dosimetry of ionizing radiation used in the treatment of cervical and uterine cancer. Thermoluminescence determination of the dose at the rectum]. Rev Med Suisse Romande 92:829-38.
Rapp L, Chen JJ (1998): The papillomavirus E6 proteins. Biochim Biophys Acta 1378:F1-19.
Reddy VG, Khanna N, Singh N (2001): Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing P53. Biochem Biophys Res Commun 282:409-15.
Roboz GJ, Dias S, Lam G, Lane WJ, Soignet SL, Warrell RP, Jr., Rafii S (2000): Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96:1525-30.
Ronco LV, Karpova AY, Vidal M, Howley PM (1998): Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 12:2061-72.
Rountree MR, Bachman KE, Herman JG, Baylin SB (2001): DNA methylation, chromatin inheritance, and cancer. Oncogene 20:3156-65.
Salazar AM, Ostrosky-Wegman P, Menendez D, Miranda E, Garcia-Carranca A, Rojas E (1997): Induction of p53 protein expression by sodium arsenite. Mutat Res 381:259-65.
Scheffner M, Munger K, Byrne JC, Howley PM (1991): The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc Natl Acad Sci U S A 88:5523-7.
Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM (1990): The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-36.
Schmitt A, Harry JB, Rapp B, Wettstein FO, Iftner T (1994): Comparison of the properties of the E6 and E7 genes of low- and high-risk cutaneous papillomaviruses reveals strongly transforming and high Rb-binding activity for the E7 protein of the low-risk human papillomavirus type 1. J Virol 68:7051-9.
Schulz EJ (1967): Arsenic as a cause of skin cancer, with notes on its occurrence in Pretoria. S Afr Med J 41:819-22.
Schwab M (1990): Amplification of the MYCN oncogene and deletion of putative tumour suppressor gene in human neuroblastomas. Brain Pathol 1:41-6.
Schwab M (1994): Human neuroblastoma: amplification of the N-myc oncogene and loss of a putative cancer-preventing gene on chromosome 1p. Recent Results Cancer Res 135:7-16.
Sedman SA, Barbosa MS, Vass WC, Hubbert NL, Haas JA, Lowy DR, Schiller JT (1991): The full-length E6 protein of human papillomavirus type 16 has transforming and trans-activating activities and cooperates with E7 to immortalize keratinocytes in culture. J Virol 65:4860-6.
Seedorf K, Krammer G, Durst M, Suhai S, Rowekamp WG (1985): Human papillomavirus type 16 DNA sequence. Virology 145:181-5.
Shao W, Fanelli M, Ferrara FF, Riccioni R, Rosenauer A, Davison K, Lamph WW, Waxman S, Pelicci PG, Lo Coco F, Avvisati G, Testa U, Peschle C, Gambacorti-Passerini C, Nervi C, Miller WH, Jr. (1998): Arsenic trioxide as an inducer of apoptosis and loss of PML/RAR alpha protein in acute promyelocytic leukemia cells. J Natl Cancer Inst 90:124-33.
Shay JW, Wright WE, Brasiskyte D, Van der Haegen BA (1993): E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts. Oncogene 8:1407-13.
Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY (1997): Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 89:3354-60.
Shimbara N, Takashina M, Sato C, Iizuka M, Kobayashi S, Tanaka K, Ichihara A (1992): c-myc expression is down-regulated by cell-cell and cell-extracellular matrix contacts in normal hepatocytes, but not in hepatoma cells. Biochem Biophys Res Commun 184:825-31.
Sinistrero G, Gola M, Sismondi P, Costanzo S, Ferraris R (1976): [Endocavitary radiotherapy of carcinoma of the cervix uteri using a modeled device and Ir-192. Computerized dosimetry]. Radiol Med (Torino) 62:369-80.
Sionov RV, Haupt Y (1999): The cellular response to p53: the decision between life and death. Oncogene 18:6145-57.
Smith-McCune K, Kalman D, Robbins C, Shivakumar S, Yuschenkoff L, Bishop JM (1999): Intranuclear localization of human papillomavirus 16 E7 during transformation and preferential binding of E7 to the Rb family member p130. Proc Natl Acad Sci U S A 96:6999-7004.
Soignet SL (2001): Clinical experience of arsenic trioxide in relapsed acute promyelocytic leukemia. Oncologist 6:11-6.
Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ, Corso D, DeBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, Warrell RP, Jr. (1998): Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 339:1341-8.
Songyang Z, Fanning AS, Fu C, Xu J, Marfatia SM, Chishti AH, Crompton A, Chan AC, Anderson JM, Cantley LC (1997): Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 275:73-7.
Spancake KM, Anderson CB, Weaver VM, Matsunami N, Bissell MJ, White RL (1999): E7-transduced human breast epithelial cells show partial differentiation in three-dimensional culture. Cancer Res 59:6042-5.
Spitz FR, Nguyen D, Skibber JM, Meyn RE, Cristiano RJ, Roth JA (1996): Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation. Clin Cancer Res 2:1665-71.
Srivastava RK, Srivastava AR, Seth P, Agrawal S, Cho-Chung YS (1999): Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RI alpha subunit: p53-independent mechanism of action. Mol Cell Biochem 195:25-36.
Stanley MA (2001): Human papillomavirus and cervical carcinogenesis. Best Pract Res Clin Obstet Gynaecol 15:663-76.
Steele C, Cowsert LM, Shillitoe EJ (1993): Effects of human papillomavirus type 18-specific antisense oligonucleotides on the transformed phenotype of human carcinoma cell lines. Cancer Res 53:2330-7.
Steller MA, Zou Z, Schiller JT, Baserga R (1996): Transformation by human papillomavirus 16 E6 and E7: role of the insulin-like growth factor 1 receptor. Cancer Res 56:5087-91.
Storey A, Banks L (1993): Human papillomavirus type 16 E6 gene cooperates with EJ-ras to immortalize primary mouse cells. Oncogene 8:919-24.
Tasken K, Solberg R, Foss KB, Skalhegg BS, Hansson V, Jahnsen T (1995): cAMP-dependent protein kinase (vertebrates). In Hardie G, Hanks S (eds): "The Protein Kinase Factsbook I." London: Academic Press.
Thomas M, Banks L (1998): Inhibition of Bak-induced apoptosis by HPV-18 E6. Oncogene 17:2943-54.
Thomas M, Banks L (1999): Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types. J Gen Virol 80 ( Pt 6):1513-7.
Thomas M, Glaunsinger B, Pim D, Javier R, Banks L (2001): HPV E6 and MAGUK protein interactions: determination of the molecular basis for specific protein recognition and degradation. Oncogene 20:5431-9.
Thomas M, Massimi P, Jenkins J, Banks L (1995): HPV-18 E6 mediated inhibition of p53 DNA binding activity is independent of E6 induced degradation. Oncogene 10:261-8.
Thomas M, Matlashewski G, Pim D, Banks L (1996a): Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene 13:265-73.
Thomas M, Matlashewski G, Pim D, Banks L (1996b): Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene 13:265-73.
Thomas M, Pim D, Banks L (1999): The role of the E6-p53 interaction in the molecular pathogenesis of HPV. Oncogene 18:7690-700.
Tong X, Howley PM (1997): The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci U S A 94:4412-7.
Trinci M, Raffetto N, Salvatori F, Trinci C (1993): [Loco-regional intra-arterial chemotherapy combined with radiotherapy in cervical carcinoma]. Radiol Med (Torino) 85:262-5.
Tsang NM, Nagasawa H, Li C, Little JB (1995): Abrogation of p53 function by transfection of HPV16 E6 gene enhances the resistance of human diploid fibroblasts to ionizing radiation. Oncogene 10:2403-8.
Turner CE (2000): Paxillin interactions. J Cell Sci 113 Pt 23:4139-40.
Ullman CG, Haris PI, Galloway DA, Emery VC, Perkins SJ (1996): Predicted alpha-helix/beta-sheet secondary structures for the zinc-binding motifs of human papillomavirus E7 and E6 proteins by consensus prediction averaging and spectroscopic studies of E7. Biochem J 319 ( Pt 1):229-39.
Um SJ, Lee SY, Kim EJ, Myoung J, Namkoong SE, Park JS (2002): Down-regulation of human papillomavirus E6/E7 oncogene by arsenic trioxide in cervical carcinoma cells. Cancer Lett 181:11-22.
Vega L, Styblo M, Patterson R, Cullen W, Wang C, Germolec D (2001): Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. Toxicol Appl Pharmacol 172:225-32.
Vikhanskaya F, Vignati S, Beccaglia P, Ottoboni C, Russo P, D'Incalci M, Broggini M (1998): Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis. Exp Cell Res 241:96-101.
Viksman MY, Liu MC, Schleimer RP, Bochner BS (1994): Application of a flow cytometric method using autofluorescence and a tandem fluorescent dye to analyze human alveolar macrophage surface markers. J Immunol Methods 172:17-24.
Vintermyr OK, Gjertsen BT, Lanotte M, Doskeland SO (1993): Microinjected catalytic subunit of cAMP-dependent protein kinase induces apoptosis in myeloid leukemia (IPC-81) cells. Exp Cell Res 206:157-61.
Wade MJ, Davis BK, Carlisle JS, Klein AK, Valoppi LM (1993): Environmental transformation of toxic metals. Occup Med 8:574-601.
Wagner AJ, Kokontis JM, Hay N (1994): Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. Genes Dev 8:2817-30.
Wahl AF, Donaldson KL, Fairchild C, Lee FY, Foster SA, Demers GW, Galloway DA (1996): Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis [see comments]. Nat Med 2:72-9.
Wajed SA, Laird PW, DeMeester TR (2001): DNA methylation: an alternative pathway to cancer. Ann Surg 234:10-20.
Wang J, Sampath A, Raychaudhuri P, Bagchi S (2001): Both Rb and E7 are regulated by the ubiquitin proteasome pathway in HPV-containing cervical tumor cells. Oncogene 20:4740-9.
Wang TS, Kuo CF, Jan KY, Huang H (1996): Arsenite induces apoptosis in Chinese hamster ovary cells by generation of reactive oxygen species. J Cell Physiol 169:256-68.
Wang TS, Shu YF, Liu YC, Jan KY, Huang H (1997): Glutathione peroxidase and catalase modulate the genotoxicity of arsenite. Toxicology 121:229-37.
Wang ZG, Rivi R, Delva L, Konig A, Scheinberg DA, Gambacorti-Passerini C, Gabrilove JL, Warrell RP, Jr., Pandolfi PP (1998): Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Blood 92:1497-504.
Wanibuchi H, Hori T, Meenakshi V, Ichihara T, Yamamoto S, Yano Y, Otani S, Nakae D, Konishi Y, Fukushima S (1997): Promotion of rat hepatocarcinogenesis by dimethylarsinic acid: association with elevated ornithine decarboxylase activity and formation of 8-hydroxydeoxyguanosine in the liver. Jpn J Cancer Res 88:1149-54.
Wanibuchi H, Yamamoto S, Chen H, Yoshida K, Endo G, Hori T, Fukushima S (1996): Promoting effects of dimethylarsinic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats. Carcinogenesis 17:2435-9.
Warner ML, Moore LE, Smith MT, Kalman DA, Fanning E, Smith AH (1994): Increased micronuclei in exfoliated bladder cells of individuals who chronically ingest arsenic-contaminated water in Nevada. Cancer Epidemiol Biomarkers Prev 3:583-90.
Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T (1998): Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell 1:507-18.
Waxman S, Anderson KC (2001): History of the development of arsenic derivatives in cancer therapy. Oncologist 6:3-10.
Wazer DE, Liu XL, Chu Q, Gao Q, Band V (1995): Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. Proc Natl Acad Sci U S A 92:3687-91.
Wei M, Wanibuchi H, Yamamoto S, Li W, Fukushima S (1999): Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats. Carcinogenesis 20:1873-6.
Werness BA, Levine AJ, Howley PM (1990): Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248:76-9.
Wicks MJ, Archer VE, Auerbach O, Kuschner M (1981): Arsenic exposure in a copper smelter as related to histological type of lung cancer. Am J Ind Med 2:25-31.
Woods DF, Hough C, Peel D, Callaini G, Bryant PJ (1996): Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J Cell Biol 134:1469-82.
Wu X, Hepner K, Castelino-Prabhu S, Do D, Kaye MB, Yuan XJ, Wood J, Ross C, Sawyers CL, Whang YE (2000a): Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc Natl Acad Sci U S A 97:4233-8.
Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q, Lasky LA (2000b): Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem 275:21477-85.
Xu C, Meikrantz W, Schlegel R, Sager R (1995): The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to apoptosis induced by DNA damage. Proc Natl Acad Sci U S A 92:7829-33.
Yager JW, Wiencke JK (1997): Inhibition of poly(ADP-ribose) polymerase by arsenite. Mutat Res 386:345-51.
Yamamoto S, Konishi Y, Matsuda T, Murai T, Shibata MA, Matsui-Yuasa I, Otani S, Kuroda K, Endo G, Fukushima S (1995): Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. Cancer Res 55:1271-6.
Yamanaka K, Katsumata K, Ikuma K, Hasegawa A, Nakano M, Okada S (2000): The role of orally administered dimethylarsinic acid, a main metabolite of inorganic arsenics, in the promotion and progression of UVB-induced skin tumorigenesis in hairless mice. Cancer Lett 152:79-85.
Yamanaka K, Ohtsubo K, Hasegawa A, Hayashi H, Ohji H, Kanisawa M, Okada S (1996): Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice. Carcinogenesis 17:767-70.
Yamanaka K, Takabayashi F, Mizoi M, An Y, Hasegawa A, Okada S (2001): Oral exposure of dimethylarsinic acid, a main metabolite of inorganic arsenics, in mice leads to an increase in 8-Oxo-2'-deoxyguanosine level, specifically in the target organs for arsenic carcinogenesis. Biochem Biophys Res Commun 287:66-70.
Yih LH, Lee TC (2000): Arsenite induces p53 accumulation through an ATM-dependent pathway in human fibroblasts. Cancer Res 60:6346-52.
Yu Y, Li CY, Little JB (1997): Abrogation of p53 function by HPV16 E6 gene delays apoptosis and enhances mutagenesis but does not alter radiosensitivity in TK6 human lymphoblast cells. Oncogene 14:1661-7.
Yu Y, Little JB (1998): p53 is involved in but not required for ionizing radiation-induced caspase-3 activation and apoptosis in human lymphoblast cell lines. Cancer Res 58:4277-81.
Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP (1997): Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci U S A 94:10907-12.
Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, Chen Z, de The H (1997): Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc Natl Acad Sci U S A 94:3978-83.
zur Hausen H (1996): Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta 1288:F55-78.

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