(3.238.173.209) 您好!臺灣時間:2021/05/16 20:05
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:黃煖喻
研究生(外文):Nuan-Yu Huang
論文名稱:探討AP-2α基因於腎細胞癌之DNA甲基化程度
論文名稱(外文):The study of DNA methylation status of activator protein-2 alpha gene in renal cell carcinoma
指導教授:許濤許濤引用關係馮思中馮思中引用關係
指導教授(外文):Todd HsuSee-Tong Pang
學位類別:碩士
校院名稱:國立臺灣海洋大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:71
中文關鍵詞:腎細胞癌抑癌基因甲基化技術基因甲基化
外文關鍵詞:RCCtumor suppression geneCOBRADNA methylation
相關次數:
  • 被引用被引用:1
  • 點閱點閱:124
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
腎細胞癌是成年人腎臟腫瘤最常見的惡性腫瘤,約佔所有成年人惡性腫瘤的2-3%。腎細胞癌的多樣性包含clear cell RCC / papillary RCC / chromophobe RCC / oncocytoma以及其它罕見的細胞型態。非轉移的腎細胞癌可以全部或部分的腎切除手術來治療,其治癒率較高,為治療首選。而已轉移的腎細胞癌可用外科手術加上標靶藥物的輔助治療來延長壽命;但一般而言轉移的腎細胞癌預後都很差,其五年的存活率也較低。由於腎細胞癌的多樣性以及有限之治療效果,因此發展腎細胞癌患者的預後預測因子以及轉移性病灶的後續治療乃刻不容緩的課題。
先前本實驗室利用Methylated-CpG island recovery assay (MIRA)的技術並結合 DNA 微陣列生物技術(DNA microarray)分析腎細胞癌異常甲基化基因的程度。經分析軟體篩選出多個重要的異常甲基化之基因(SFRP1、EDNRB、MSH2、AP-2α、MT1G、NLRC5...等)。報導指出SFRP1、EDNRB和MT1G於腎細胞癌中有高度甲基化發生。然而AP-2α在腎細胞癌不曾被報導過有關基因甲基化的現象。AP-2α為轉錄因子且會活化p53或p21WAF1/CIP1 的基因表現,並且會造成細胞凋亡,而AP-2α在許多癌症已被證實是抑癌基因。
本實驗利用Real-time quantitative PCR分析腎細胞癌組織AP-2α基因,發現此基因表現量於各類型癌組織中,除了oncocytoma為良性腫瘤外,其餘均明顯下降;包含clear cell RCC 89% (42/47)、papillary RCC 70% (7/10)、chromophobe RCC 44% (4/9)以及oncocytoma 0% (0/3);再藉Immunohistochemistry發現腎細胞癌組織中AP-2α蛋白表現量也有明顯下降的趨勢。吾等近一步利用combined bisulfite restriction analysis (COBRA)分析腎細胞癌組織之Ap-2α甲基化程度,結果各腫瘤的甲基化程度為clear cell RCC 81% (34/42)、papillary RCC 83% (5/6)、chromophobe RCC 0% (0/8) 以及oncocytoma 0% (0/3)。故Ap-2α基因在clear cell RCC 以及papillary RCC均呈現高度甲基化現象,這和其基因表現量也較低是一致的;然而在惡性度較低的 chromophobe RCC 以及良性腫瘤oncocytoma則沒有甲基化現象,我們推測Ap-2α甲基化的程度和腎細胞癌腫瘤的惡性程度有關。
本研究我們發現Ap-2α的基因表現量在RCC亦較低,而且和甲基化程度有關。未來我們可繼續研究探討Ap-2α甲基化程度作為腎細胞癌分子診斷工具來輔助臨床治療。
Renal cell carcinoma (RCC) is the most common kidney cancer noted in adult population, accounting for 2%-3% of all adult malignant tumors. Renal cell carcinoma can further classify into different tissue subtypes including chromophobe, oncocytoma and other renal cell types. Surgical removal of the kidney (all or partially) is the treatment of choice for non-metastasis tumor, which possess a higher chance of cure after surgery. For metastatic RCC, targeted therapy with tyrosine kinase or mTOR inhibitors can prolong the survival of the patients. However, not all RCC cell types can be benefit from these treatments. The mechanism of the pathogenesis of RCC is still not fully elucidated. Our previous studies using Methylated-CpG island recovery assay (MIRA) and DNA microarray technology have identified novel methylated DNAs that may play potential role in RCC pathogenesis. Many novel methylated DNAs can be detected using our genome-wide analysis approach. These included SFRP1, EDNRB, MSH2, AP-2α etc. The AP-2α gene can regulate the expression of p53 and p21WAF1/CIP1 and induce the cell apoptosis. Moreover, AP-2α also have been proven to be a cancer suppression gene. In this study, we have correlated the relationship of AP-2α gene expression and its DNA methylation level in RCC. The expression level of AP-2α was decreased in all subtype of RCC, except oncocytoma, using real-time quantitative PCR analysis. The percentage of tumor with a lower gene expression was: clear cell (89%,42/47), papillary (70%, 7/10), chromophobe (44%, 4/9), and oncocytoma (0%, 0/3). In addition, the AP-2α protein expression was also markedly decreased in RCC using immunohistochemistry analysis. We further analyzed the regulation of Ap-2α expression using combined bisulfite restriction analysis (COBRA). The percentage of DNA methylation of Ap-2α gene in different RCC subtype was: 81% (34/42) for clear cell, 83% (5/6) for papillary, 0% (0/8) for chromophobe, and 0% (0/3) for oncocytoma. Our results showed that the DNA of clear cell and papillary RCC were highly methylated and they were compatible with lower AP-2α gene expression. However, chromophobe and oncocytoma subtypes did not display any DNA methylation phenomenon probably because they are low grade renal cell carcinoma. Our study has shown, as compare to its normal counterpart, that Ap-2α gene expression was lower in several subtypes of RCC. In addition, Ap-2α gene expression seems to be controlled through DNA methylation. Our data indicates that Ap-2α may play a role in the pathogenesis of RCC. Further analysis of this gene will help us to develop new method for the diagnosis and treatment of RCC.
致謝…………………………………………………………………………i
摘要………………………………………………………………………iii
Abstract……………………………………………………………………v
目錄………………………………………………………………………vii
表目錄……………………………………………………………………x
圖目錄……………………………………………………………………xi
緒論………………………………………………………………………1
1-1 腎細胞癌簡介( Renal cell carcinoma;RCC )……………………1
1-2 腎細胞癌分類……………………………………………………4
1-3 腎細胞癌致病的分子機轉………………………………………8
1-4 DNA甲基化與癌症所扮演的角色………………………………9
1-5 轉錄因子AP-2α…………………………………………………13
材料與方法………………………………………………………………16
2-1研究材料…………………………………………………………16
2-1-1腎細胞癌檢體來源………………………………………16
2-2分析軟體…………………………………………………………16
2-2-1基因分析軟體……………………………………………16
2-2-2 primer設計軟體及primer序列…………………………16
2-3試劑套組及一般藥品……………………………………………17
2-3-1試劑套組…………………………………………………17
2-3-2一般藥品…………………………………………………18
2-4藥品配方…………………………………………………………19
2-5儀器設備…………………………………………………………20
2-6實驗方法…………………………………………………………21
2-6-1 DNA微陣列生物技術結果分析方法…………………21
2-6-2腎細胞癌組織之RNA萃取………………………………22
2-6-3反轉錄聚合酶連鎖反應(Reverse Transcription-Polymerase Chain Reaction;RT-PCR)……………………………………23
2-6-4即時定量聚合酶鏈鎖反應(Real-time quantitative PCR)25
2-6-5組織微陣列生物晶片 (tissue microarray)………………26
2-6-6免疫染色(Immunohistochemistry; IHC)…………………27
2-6-7腎細胞癌組織之DNA萃取………………………………28
2-6-8以Combined Bisulfite Restriction Analysis(COBRA)分析DNA甲基化程度(圖九)(Xiong and Laird 1997)………………29
2-6-8-1 DNA經重亞硫酸鹽(sodium bisulfite)置換以及PCR反應………………………………………………………30
2-6-8-2 DNA洋菜膠電泳…………………………………32
2-6-8-3洋菜膠體的萃取方法(Gel extraction)……………32
2-6-8-4以限制酶酵素BSTU1反應確認甲基化情形………………32
2-6-8-5以10% non-denaturing polyacrylamide gel判定甲基
化結果……………………………………………………33
2-6-9統計分析…………………………………………………34
結果與討論………………………………………………………………35
3-1 DNA微陣列生物技術結果分析……………………………35
3-1-1利用分析軟體找尋Ap-2α基因…………………………35
3-1-2利用Signal Map分析Ap-2α基因起動子甲基化區域………………36
3-2利用分生技術分析Ap-2α基因甲基化情形 (圖十二)…………39
3-2-1以即時定量聚合酶鏈鎖反應分析腎細胞癌Ap-2α mRNA
表現量…………………………………………………………40
3-2-2以組織微陣列技術並結合免疫染色偵測AP-2α蛋白的表
現量…………………………………………………………41
3-2-3以COBRA技術分析Ap-2α DNA甲基化程度…………44
結論………………………………………………………………………50
參考文獻…………………………………………………………………52
Andrews, D. W., C. B. Scott, P. W. Sperduto, A. E. Flanders, L. E. Gaspar,
M. C. Schell, M. Werner-Wasik, W. Demas, J. Ryu, J. P. Bahary, L.
Souhami, M. Rotman, M. P. Mehta, and W. J. Curran, Jr. 2004.
Whole brain radiation therapy with or without stereotactic
radiosurgery boost for patients with one to three brain metastases:
phase III results of the RTOG 9508 randomised trial. Lancet
363:1665-1672.
Anttila, M. A., J. K. Kellokoski, K. I. Moisio, P. J. Mitchell, S. Saarikoski,
K. Syrjanen, and V. M. Kosma. 2000. Expression of transcription
factor AP-2alpha predicts survival in epithelial ovarian cancer. Br J
Cancer 82:1974-1983.
Baldewijns, M. M., I. J. van Vlodrop, P. B. Vermeulen, P. M. Soetekouw,
M. van Engeland, and A. P. de Bruine. 2010. VHL and HIF
signalling in renal cell carcinogenesis. J Pathol 221:125-138.
Banks, R. E., P. Tirukonda, C. Taylor, N. Hornigold, D. Astuti, D. Cohen,
E. R. Maher, A. J. Stanley, P. Harnden, A. Joyce, M. Knowles, and P.
J. Selby. 2006. Genetic and epigenetic analysis of von Hippel-Lindau
(VHL) gene alterations and relationship with clinical variables in
sporadic renal cancer. Cancer Res 66:2000-2011.
Bar-Eli, M. 2001. Gene regulation in melanoma progression by the AP-2
transcription factor. Pigment Cell Res 14:78-85.
Berger, A. J., D. W. Davis, C. Tellez, V. G. Prieto, J. E. Gershenwald, M.
M. Johnson, D. L. Rimm, and M. Bar-Eli. 2005. Automated
quantitative analysis of activator protein-2alpha subcellular
expression in melanoma tissue microarrays correlates with survival
prediction. Cancer Res 65:11185-11192.
Bosher, J. M., N. F. Totty, J. J. Hsuan, T. Williams, and H. C. Hurst. 1996.
A family of AP-2 proteins regulates c-erbB-2 expression in
mammary carcinoma. Oncogene 13:1701-1707.
Cheng, C., K. Ying, M. Xu, W. Zhao, Z. Zhou, Y. Huang, W. Wang, J. Xu,
L. Zeng, Y. Xie, and Y. Mao. 2002. Cloning and characterization of
a novel human transcription factor AP-2 beta like gene (TFAP2BL1).
Int J Biochem Cell Biol 34:78-86.
Cho, E., H. O. Adami, and P. Lindblad. 2011. Epidemiology of renal cell
cancer. Hematol Oncol Clin North Am 25:651-665.
Chow, W. H., S. S. Devesa, J. L. Warren, and J. F. Fraumeni, Jr. 1999.
Rising incidence of renal cell cancer in the United States. JAMA
281:1628-1631.
Chow, W. H., L. M. Dong, and S. S. Devesa. 2010. Epidemiology and risk
factors for kidney cancer. Nat Rev Urol 7:245-257.
Cohen, H. T. and F. J. McGovern. 2005. Renal-cell carcinoma. N Engl J
Med 353:2477-2490.
Costello, J. F. and C. Plass. 2001. Methylation matters. J Med Genet
38:285-303.
Delahunt, B., J. M. Kittelson, M. R. McCredie, A. E. Reeve, J. H. Stewart,
and A. M. Bilous. 2002. Prognostic importance of tumor size for
localized conventional (clear cell) renal cell carcinoma: assessment
of TNM T1 and T2 tumor categories and comparison with other
prognostic parameters. Cancer 94:658-664.
Devesa, S. S., D. T. Silverman, J. K. McLaughlin, C. C. Brown, R. R.
Connelly, and J. F. Fraumeni, Jr. 1990. Comparison of the
descriptive epidemiology of urinary tract cancers. Cancer Causes
Control 1:133-141.
Esteller, M. 2002. CpG island hypermethylation and tumor suppressor
genes: a booming present, a brighter future. Oncogene
21:5427-5440.
Gaynor, R. B., C. Muchardt, Y. R. Xia, I. Klisak, T. Mohandas, R. S.
Sparkes, and A. J. Lusis. 1991. Localization of the gene for the
DNA-binding protein AP-2 to human chromosome 6p22.3-pter.
Genomics 10:1100-1102.
Gee, J. M., J. F. Robertson, I. O. Ellis, R. I. Nicholson, and H. C. Hurst.
1999. Immunohistochemical analysis reveals a tumour
suppressor-like role for the transcription factor AP-2 in invasive
breast cancer. J Pathol 189:514-520.
Gee, M. S., C. J. Sarkisian, and W. S. el-Deiry. 1998. Identification of a
novel AP-2 consensus DNA binding site. Biochem Biophys Res
Commun 243:307-316.
Gonzalgo, M. L., S. Yegnasubramanian, G. Yan, C. G. Rogers, T. L. Nicol,
W. G. Nelson, and C. P. Pavlovich. 2004. Molecular profiling and
classification of sporadic renal cell carcinoma by quantitative
methylation analysis. Clin Cancer Res 10:7276-7283.
Gowher, H., K. Liebert, A. Hermann, G. Xu, and A. Jeltsch. 2005.
Mechanism of stimulation of catalytic activity of Dnmt3A and
Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol
Chem 280:13341-13348.
Heimberger, A. B., E. C. McGary, D. Suki, M. Ruiz, H. Wang, G. N. Fuller,
and M. Bar-Eli. 2005. Loss of the AP-2alpha transcription factor is
associated with the grade of human gliomas. Clin Cancer Res
11:267-272.
Hilger-Eversheim, K., M. Moser, H. Schorle, and R. Buettner. 2000.
Regulatory roles of AP-2 transcription factors in vertebrate
development, apoptosis and cell-cycle control. Gene 260:1-12.
Jemal, A., T. Murray, E. Ward, A. Samuels, R. C. Tiwari, A. Ghafoor, E. J.
Feuer, and M. J. Thun. 2005. Cancer statistics, 2005. CA Cancer J
Clin 55:10-30.
Jemal, A., R. Siegel, E. Ward, Y. Hao, J. Xu, and M. J. Thun. 2009. Cancer
statistics, 2009. CA Cancer J Clin 59:225-249.
Kagara, I., H. Enokida, K. Kawakami, R. Matsuda, K. Toki, H. Nishimura,
T. Chiyomaru, S. Tatarano, T. Itesako, K. Kawamoto, K. Nishiyama,
N. Seki, and M. Nakagawa. 2008. CpG hypermethylation of the
UCHL1 gene promoter is associated with pathogenesis and poor
prognosis in renal cell carcinoma. J Urol 180:343-351.
Karjalainen, J. M., J. K. Kellokoski, M. J. Eskelinen, E. M. Alhava, and V.
M. Kosma. 1998. Downregulation of transcription factor AP-2
predicts poor survival in stage I cutaneous malignant melanoma. J
Clin Oncol 16:3584-3591.
Kawamoto, K., H. Hirata, N. Kikuno, Y. Tanaka, M. Nakagawa, and R.
Dahiya. 2008. DNA methylation and histone modifications cause
silencing of Wnt antagonist gene in human renal cell carcinoma cell
lines. Int J Cancer 123:535-542.
Kuan, P. F., H. Chun, and S. Keles. 2008. CMARRT: a tool for the analysis
of ChIP-chip data from tiling arrays by incorporating the correlation
structure. Pac Symp Biocomput:515-526.
Lam, J. S., A. S. Belldegrun, and A. J. Pantuck. 2006. Long-term outcomes
of the surgical management of renal cell carcinoma. World J Urol
24:255-266.
Lau, W. K., J. C. Cheville, M. L. Blute, A. L. Weaver, and H. Zincke. 2002.
Prognostic features of pathologic stage T1 renal cell carcinoma after
radical nephrectomy. Urology 59:532-537.
Lindblad, P. 2004. Epidemiology of renal cell carcinoma. Scand J Surg
93:88-96.
Linehan, W. M., J. Vasselli, R. Srinivasan, M. M. Walther, M. Merino, P.
Choyke, C. Vocke, L. Schmidt, J. S. Isaacs, G. Glenn, J. Toro, B.
Zbar, D. Bottaro, and L. Neckers. 2004. Genetic basis of cancer of
the kidney: disease-specific approaches to therapy. Clin Cancer Res
10:6282S-6289S.
Linehan, W. M., M. M. Walther, and B. Zbar. 2003. The genetic basis of
cancer of the kidney. J Urol 170:2163-2172.
Lipponen, P., S. Aaltomaa, J. Kellokoski, M. Ala-Opas, and V. Kosma.
2000. Expression of activator protein 2 in prostate cancer is related
to tumor differentiation and cell proliferation. Eur Urol 37:573-578.
Ljungberg, B., D. C. Hanbury, M. A. Kuczyk, A. S. Merseburger, P. F.
Mulders, J. J. Patard, and I. C. Sinescu. 2007. Renal cell carcinoma
guideline. Eur Urol 51:1502-1510.
McPherson, L. A., A. V. Loktev, and R. J. Weigel. 2002. Tumor suppressor
activity of AP2alpha mediated through a direct interaction with p53.
J Biol Chem 277:45028-45033.
McPherson, L. A. and R. J. Weigel. 1999. AP2alpha and AP2gamma: a
comparison of binding site specificity and trans-activation of the
estrogen receptor promoter and single site promoter constructs.
Nucleic Acids Res 27:4040-4049.
Minervini, R., A. Minervini, N. Fontana, C. Traversi, and R. Cristofani.
2000. Evaluation of the 1997 tumour, nodes and metastases
classification of renal cell carcinoma: experience in 172 patients.
BJU Int 86:199-202.
Moch, H., T. Gasser, M. B. Amin, J. Torhorst, G. Sauter, and M. J.
Mihatsch. 2000. Prognostic utility of the recently recommended
histologic classification and revised TNM staging system of renal
cell carcinoma: a Swiss experience with 588 tumors. Cancer
89:604-614.
Mohibullah, N., A. Donner, J. A. Ippolito, and T. Williams. 1999. SELEX
and missing phosphate contact analysis reveal flexibility within the
AP-2[alpha] protein: DNA binding complex. Nucleic Acids Res
27:2760-2769.
Morris, M. R., D. Gentle, M. Abdulrahman, E. N. Maina, K. Gupta, R. E.
Banks, M. S. Wiesener, T. Kishida, M. Yao, B. Teh, F. Latif, and E.
R. Maher. 2005. Tumor suppressor activity and epigenetic
inactivation of hepatocyte growth factor activator inhibitor type
2/SPINT2 in papillary and clear cell renal cell carcinoma. Cancer
Res 65:4598-4606.
Morrissey, C., A. Martinez, M. Zatyka, A. Agathanggelou, S. Honorio, D.
Astuti, N. V. Morgan, H. Moch, F. M. Richards, T. Kishida, M. Yao,
P. Schraml, F. Latif, and E. R. Maher. 2001. Epigenetic inactivation
of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and
papillary renal cell carcinoma. Cancer Res 61:7277-7281.
Motzer, R. J., N. H. Bander, and D. M. Nanus. 1996. Renal-cell carcinoma.
N Engl J Med 335:865-875.
Okano, M., S. Xie, and E. Li. 1998. Cloning and characterization of a
family of novel mammalian DNA (cytosine-5) methyltransferases.
Nat Genet 19:219-220.
Pellikainen, J., A. Naukkarinen, K. Ropponen, J. Rummukainen, V. Kataja,
J. Kellokoski, M. Eskelinen, and V. M. Kosma. 2004. Expression of
HER2 and its association with AP-2 in breast cancer. Eur J Cancer
40:1485-1495.
Pischon, T., P. H. Lahmann, H. Boeing, A. Tjonneland, J. Halkjaer, K.
Overvad, K. Klipstein-Grobusch, J. Linseisen, N. Becker, A.
Trichopoulou, V. Benetou, D. Trichopoulos, S. Sieri, D. Palli, R.
Tumino, P. Vineis, S. Panico, E. Monninkhof, P. H. Peeters, H. B.
Bueno-de-Mesquita, F. L. Buchner, B. Ljungberg, G. Hallmans, G.
Berglund, C. A. Gonzalez, M. Dorronsoro, A. B. Gurrea, C. Navarro,
C. Martinez, J. R. Quiros, A. Roddam, N. Allen, S. Bingham, K. T.
Khaw, R. Kaaks, T. Norat, N. Slimani, and E. Riboli. 2006. Body
size and risk of renal cell carcinoma in the European Prospective
Investigation into Cancer and Nutrition (EPIC). Int J Cancer
118:728-738.
Rauch, T., H. Li, X. Wu, and G. P. Pfeifer. 2006. MIRA-assisted
microarray analysis, a new technology for the determination of DNA
methylation patterns, identifies frequent methylation of
homeodomain-containing genes in lung cancer cells. Cancer Res
66:7939-7947.
Rauch, T. A. and G. P. Pfeifer. 2009. The MIRA method for DNA
methylation analysis. Methods Mol Biol 507:65-75.
Rini, B. I., S. C. Campbell, and B. Escudier. 2009. Renal cell carcinoma.
Lancet 373:1119-1132.
Ropponen, K. M., J. K. Kellokoski, P. K. Lipponen, T. Pietilainen, M. J.
Eskelinen, E. M. Alhava, and V. M. Kosma. 1999. p22/WAF1
expression in human colorectal carcinoma: association with p53,
transcription factor AP-2 and prognosis. Br J Cancer 81:133-140.
Ropponen, K. M., J. K. Kellokoski, R. T. Pirinen, K. I. Moisio, M. J.
Eskelinen, E. M. Alhava, and V. M. Kosma. 2001. Expression of
transcription factor AP-2 in colorectal adenomas and
adenocarcinomas; comparison of immunohistochemistry and in situ
hybridisation. J Clin Pathol 54:533-538.
Ruiz, M., P. Troncoso, C. Bruns, and M. Bar-Eli. 2001. Activator protein
2alpha transcription factor expression is associated with luminal
differentiation and is lost in prostate cancer. Clin Cancer Res
7:4086-4095.
Toedling, J., O. Skylar, T. Krueger, J. J. Fischer, S. Sperling, and W. Huber.
2007. Ringo--an R/Bioconductor package for analyzing ChIP-chip
readouts. BMC Bioinformatics 8:221.
Tummala, R., R. A. Romano, E. Fuchs, and S. Sinha. 2003. Molecular
cloning and characterization of AP-2 epsilon, a fifth member of the
AP-2 family. Gene 321:93-102.
Wajapeyee, N. and K. Somasundaram. 2003. Cell cycle arrest and
apoptosis induction by activator protein 2alpha (AP-2alpha) and the
role of p53 and p21WAF1/CIP1 in AP-2alpha-mediated growth
inhibition. J Biol Chem 278:52093-52101.
Williams, T. and R. Tjian. 1991a. Analysis of the DNA-binding and
activation properties of the human transcription factor AP-2. Genes
Dev 5:670-682.
Williams, T. and R. Tjian. 1991b. Characterization of a dimerization motif
in AP-2 and its function in heterologous DNA-binding proteins.
Science 251:1067-1071.
Williamson, J. A., J. M. Bosher, A. Skinner, D. Sheer, T. Williams, and H.
C. Hurst. 1996. Chromosomal mapping of the human and mouse
homologues of two new members of the AP-2 family of transcription
factors. Genomics 35:262-264.
Wolffe, A. P. and M. A. Matzke. 1999. Epigenetics: regulation through
repression. Science 286:481-486.
Xiong, Z. and P. W. Laird. 1997. COBRA: a sensitive and quantitative
DNA methylation assay. Nucleic Acids Res 25:2532-2534.
Zeng, Y. X., K. Somasundaram, and W. S. el-Deiry. 1997. AP2 inhibits
cancer cell growth and activates p21WAF1/CIP1 expression. Nat
Genet 15:78-82.
Zisman, A., A. J. Pantuck, F. Dorey, D. H. Chao, B. J. Gitlitz, N. Moldawer,
D. Lazarovici, J. B. deKernion, R. A. Figlin, and A. S. Belldegrun.
2002. Mathematical model to predict individual survival for patients
with renal cell carcinoma. J Clin Oncol 20:1368-1374.
Zou, L., Y. Sun, M. Wang, and Q. Zhan. 2011. Aurora-A interacts with
AP-2alpha and down regulates its transcription activity. PLoS One
6:e23110.
行政院衛生署
(http://www.bhp.doh.gov.tw/bhpnet/portal/Them.aspx?No=200712250019)
台灣癌證登記小組(http://tcr.cph.ntu.edu.tw/main.php?Page=A5B2)
台灣癌症防治網(http://cisc.twbbs.org/discover.php)

連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊