跳到主要內容

臺灣博碩士論文加值系統

(18.97.14.87) 您好!臺灣時間:2024/12/05 22:23
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:邱鳳蘭
研究生(外文):Feng-Lan Chiu
論文名稱:EB病毒核抗原-1氮端部位可抑制因神經膠原致癌基因過度表現之人類乳癌細胞的轉型特性
論文名稱(外文):Repression of transforming effect of the HER-2/neu oncogene by the N-terminal domain of the EBNA-1 in breast cancer cells
指導教授:高銘欽高銘欽引用關係
指導教授(外文):Ming-Ching Kao
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:64
中文關鍵詞:神經膠原致癌基因EB病毒核抗原-1人類乳癌細胞噬菌體T7標籤
外文關鍵詞:HER-2/neuEBNA1human breast cancerT7Tag
相關次數:
  • 被引用被引用:1
  • 點閱點閱:138
  • 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:1
神經膠原致癌基因表現的調控失當與許多人類的癌症有著密切關係,例如臨床上發現近30 %乳癌病患有此現象且預後很差。本實驗室發現EB病毒核抗原-1具有抑制HER-2/neu啟動子的能力,但EB病毒核抗原-1具有將細胞轉形的能力,故進一步將EB病毒核抗原-1作刪除突變結果顯示在EB病毒核抗原-1氮端1至86個胺基酸的片段具有抑制HER-2/neu啟動子活性的能力,然由於此片段太小不易利用西方墨點法偵測,故將此片段接上一個T7Tag標籤,進而研究EBNA1-NT接上T7Tag (稱之EBNA1-NT-T7Tag) 後,對於HER-2/neu啟動子活性之影響。將EBNA1-NT-T7Tag暫時轉染至NIH3T3細胞後發現此片段仍保有抑制HER-2/neu啟動子活性的能力,接著將此片段永久轉染至HER-2/neu過度表現的人類乳癌細胞MDA-MB453與HER-2/neu低表現的人類乳癌細胞MDA-MB231後觀察此片段對內生性p185HER-2/neu是否具有專一性的抑制作用,結果發現此片段並未明顯減低p185HER-2/neu的表現量,但是可以觀察到對p185HER-2/neu磷酸化明顯的改變,而磷酸化即是HER-2/neu轉形作用要素之一。顯然,EBNA1-NT-T7Tag在永久轉染的MDA-MB453細胞中仍可以抑制p185HER-2/neu的磷酸化作用,進而導正其轉形能力。本實驗結果建立一易於檢測EBNA1-NT的方式,並發現EBNA1可減少HER-2/neu 磷酸化的現象,進而提供了EBNA1可能成為具有HER-2/neu 致癌基因過度表現病人的臨床藥物。
The HER-2/neu protooncogene was known to overexpressed in approximately 30% of breast cancer patients and correlated with poor survival. Repression of HER-2/neu overexpression suppressed the malignant phenotype of HER-2/neu-overexpressing cancers. In our previous study, we found that the N-terminal 86-amino-acid only of the Epstein-Barr virus nuclear antigen-1(EBNA1-NT) could act as a transforming suppressor of the HER-2/neu oncogene. However, the EBNA1-NT peptide is rather small and difficult to be analyzed by Western blot. Therefore, we established in this study a EBNA1-NT-T7Tag construct by adding a T7Tag, which is easily detected by a commercial available anti-T7Tag antibody, to the N-terminal end of the EBNA1-NT. This EBNA1-NT-T7Tag clone was found to reserve the same repressing effect as that of EBNA1-NT on the HER-2/neu promoter in the transfection experiment using NIH3T3 as recepient cells. Furthermore, the endogenous modulation of the HER-2/neu by EBNA1-NT-T7Tag was investigated by stable transfecting EBNA1-NT-T7Tag into the HER-2/neu-overexpressing human breast cancer MDA-MB453 cells and the low HER-2/neu-expressing human breast cancer MDA-MB231 cells. Although the level of p185 HER-2/neu was not dramatically reduced in MDA-MB453 cells with EBNA1-NT-T7Tag, the phosphorylated from of p185 HER-2/neuwas apparently decreased. In addition, the morphology of MDA-MB453 cells were reversed by the EBNA1-NT-T7Tag. The data shown that the EBNA1-NT-T7Tag could downregulate HER-2/neu oncogne. Taken together, these results may provide a therapeutic benefit for HER-2/neu-overexpressing human cancers.
圖目錄……………………………………………………………iii
中文摘要…………………………………………………………iv
英文摘要…………………………………………………………v
第一章 緒論...................................................................................1
第一節 研究緣起及目的.........................................................1
第二節 文獻回顧...........................................................................3
壹、神經膠原致癌基因................................................................3
貳、神經膠原致癌基因與癌症.......................................6
參、EB病毒核抗原-1.....................................................11
第三節 研究方法及流程............................................................16
第二章 實驗材料及方法.............................................................18
第一節 實驗材料及儀器.............................................................18
第二節 實驗材料及方法.............................................................21
第三章 實驗結果.........................................................................27
壹、 EB病毒核抗原-1氮端胺酸1至86及38至86接有
T7Tag標籤片段轉殖於含新黴素抗藥基因的質
體pcDNA3 ........................................................................27
貳、 neu基因的轉錄表現受EB病毒核抗原-1氮端胺
酸1至86及38至86接有T7Ta標籤片段的抑制情形..........28
參、 pcDNA3-EBNA-NT-5''T7Tag在細胞中表現情形..............30
肆、 EB病毒核抗原-1氮端接有T7Tag標籤片段抑制
neu基因的轉錄表現之劑量依存性(dose dependence )
分析....................................................................................31
伍、 EB病毒核抗原-1氮端接有T7Tag標籤片段轉染
MDA-MB453、MDA-MB231細胞後 之形態變異
(morphology change).........................................................32
陸、EB病毒核抗原-1氮端的 5''端接有T7Tag之片段產
物抑制內生性p185 HER-2/neu產量的情形......................33
第四章 討論...............................................................................35
參考文獻....................................................................................43
附錄............................................................................................52
圖目錄
圖1-1實驗流程圖(1)..................................................................16
圖1-2實驗流程圖(2)..................................................................17
圖3-1(A)EB病毒核抗原-1氮端重組DNA............................29
圖3-1(B)neu起動子活性受EB病毒核抗原-1氮端重
組基因產物抑制情形............................................29
圖3-2 EB病毒核抗原-1氮端重組DNA於BOSC-23
細胞中之表現..................................................................30
圖3-3 neu起動子EB病毒核抗原-1氮端5''-T7Tag之胜
產物抑制之劑量依存性(dose dependent)分析...........31
圖3-4 EB病毒核抗原-1氮端5''T7Tag以及EB病毒核
抗原-1氮端轉染至MDA-MB453細胞後的細胞
型態變異( morphology change) ......................................32
圖3-5 (A)西方點墨法測定野生型及永久性轉染EB病
毒核抗原-1突變型EBNA1-NT5''T7Tag之
MDA-MB453細胞的內生性p185表現情形.............33
圖3-5 (B)西方點墨法測定野生型及永久性轉染EB病
毒核抗原-1突變型EBNA1-NT5''T7Tag之
MDA-MB453細胞的內生性p185磷酸化情形..........34
圖4-1 neu啟動子抑制蛋白的作用位置示意圖........................40
Arteaga, C. L., Winnier, A. R., Poirier, M. C., Lopez-Larraza, D. M., Shawver, L. K., hurd, S. D. And Stewart, S. J. (1994) Cancer Res 54, 3758-3765.
Baer, R., A. T. Bankier, M. D. Biggin, P. L. Deiniger, P. J. Farrell, T. J. Gibson, G. Hatfull, G. S. Hudson, S. C. Satchwell, C. Seguin, P. S. Tuffnell and B. G. Barrell. (1984) DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310, 207-211.
Bargmann, C. I., Hung, M. C. & Weinberg, R. A. (1986) The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319, 226-230.
Berchuck, A., Kamel, A., Whitaker, R., Kerns, B., Olt, G., Kinney, R., Soper, J. T., Dodge, R., Clarke-Pearson, D. L., Marks, P., Mckenzie, S., Yin, S. & Bast, R. C. J. (1990) Cancer Res. 50, 4087-4091.
Bertram, J., Killian, M., Brysch, W., Schlingensiepen, K. H. & Kneba, M. (1994) Reduction of erbB2 gene product in mammary carcinoma cell lines by erbB2 mRNA-specific and tyrosine kinase consensus phosphorothioate antisense oligonucliotides. Biochim. Biophys. Res. Commm. 200, 661-667.
Cantley, L. C., Auger, K. R. Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R. & Soltoff, S. (1991) Oncogenes and signal transduction. Cell 64, 281-302.
Chen, H. and Hung, M.C. (1997) Involvement of co-activator p300 in the
transcriptional regulation the HER-2/neu gene. J. Biol. Chem, 272, 6101-
6104.
Dickman, S.(1998)Antibody stage a comeback in cancer treatment. Science 280, 1196-1197
Dougall, W. C., Qian, X., Peterson, N. C. Miller, M. J. Samanta, A. & Greene, M. I. (1994) The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies. Oncogene 9, 2109-2123.
Dsly, R. J.Binder, M. D. & Sutherland, R. L. (1994) Overexpression of the Grb2 gene in human breast cancer cell lines. Oncogene 9, 2723-2727.
D''souza, B. & Taylor-Papdimitriou, J. (1994) Overexpression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-cadherin gene. Proc. Natl. Acad. Sci. USA 91,7202-7206.
Durrant, L. G.(1997)Cancer vaccines. Anti-cancer drugs 8, 727-733.
Fahraeus, R. et al. (1988) Int. J. Cancer 42, 329-338
Falls, D. L., Rosen, K. M., Corfas, G., Lane, W. S. and Fischbach, G. D. (1993) ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family. Cell 72, 801-8015
Fisher, N., Jremmer, E., Lautscham, G., Mueller-Lanzsch, N. and Grasser, F. A. (1997) Epstein-Barr virus antigen 1 forms a complex with the nuclear transproter karyopherin α2. J. Biol. Chem. 272, 3999-4005.
Frappier, L. and Goldsmith, K. and Bendell, L. (1994) Stablization of the EBNA1 protein on the Epstein-Barr virus latent origin of DNA replication by a DNA looping mechanism. J Biol. Chem. 269, 1057-1062.
Gassmann, M., Casagranda, F. Orioll, D. Simon, H. Lai, C. Klein, R. & Lemke, G. (1995) Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature 378, 390-394.
Gee, J. E. Yen, R. L., Hung M. C. & Hogan, M. E. (1994) Triple formation at the rat neu oncogene promoter. Gene 149, 109-114.
Gonzalez, G. A. and Montminy, M. R. (1989) Cyclic AMP stimulates somatostain gene transcription by phosphorylation of CREB at serine. Cell 59, 675-680.
Gorlich, D. and Mattaj, I. W. (1996) Nucleocytoplasmic Transport. Science 271, 1513-1518.
Gotoh, N., Tojo, A., Muroya, K., Hashimoto, Y., Hattori, S., Nakamura, S., Tskenawa, T., Yazaki, Y. & Shibuya, M. (1994) Epidermal growth factor-receptor mutant lacking the autophosphorylation sites induces phosphorylation of Shc protein and Shc-Grb2/ASH association and retains mitogenic activity. Proc. Natl. Acaad. Sci. USA 91, 167-171.
Gullick, W. J.,(1990) The role of the epidermal growth factor receptor and the c-erbB-2 protein in breast. Int. J. Cancer (suppl.) 5, 55-61.
Gullick, W. J., Love, S. B., Wreght, C. (1991) c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and univolved lymph nodes. Br. J. Cancer 63, 434-440.
Gusterson, B. A., Gelber, R. D., Coldhirsch, A., Price, K. N., Save-Soderborgh, J.( 1992) Prognostic importance of c-erbB-2 expression in breast cancer. J. Clin. Oncol. 10, 1049-1056.
Hancock, M. C., Langton, B. C., Chan, T., Toy, P., Monahan, J. J., Michak, R. P. And Shawver, L. K.(1991) A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis- diamminedichloroplatinum against human breast and ovarian tumor cell lines. Cancer Res 51, 4575-4580.
Hearing, J. C. and Levine, A. J. (1985) The Epstein-Barr virus nuclear antigen (BamHI K antigen) is a single-strand DNA binding phosphoprotein. J. Virol. 145, 105-116.
Holmes, W. E., Sliwkowski, M. X., Akita, R. W., Hinzel, W. J., Lee, J., Park, J. W., Yansura, D., Abadi, N., Raab, H., Lewis, G. D., Sgepard, H. M., Kuang, W. J., Wood, W. I., Goeddel, D. V. & Vandlen, R. L. (1992) Identification of Heregulin, a specific activator of p185erbB2. Science 256, 1205-1210.
Hudziak, R. M., Lewis, G. D., Winget, M., Fendly, B. M., Shepard, H. M. and Ullrich, A. (1989) Monoclonal antibody has antiproliferative effects in vitro and senitizes human breast tumor cells to tumor necrosis factor. Mol. Cell Biol. 9, 1165-1172.
Hung, M. C., Yan, D. H. & Zhao, X. (1989) Amplification of the proto-neu oncogene facilitates oncogenic activation by a single point mutation. Proc. Natl. Acad. Sic. USA 86, 2545-2548.
Hunter, T., and Karin, M. (1992) The regulation of transcription by
phosphorylation. Cell 70, 375-387.
Indolfi, C., Chiariello, M. and Avvedimento, E. V. (1996) Selective gene therapy for proliferative disorders: Sence and Antisense. Nature Medicine. 2 (6), 634-635.
Inoue, N., Harada, S., Honma, T., Kitamura, T. and Yanagi, K. (1991) The domain of Epstein-Barr virus nuclear antigen 1 essential for binding to oriP region has a sequence fitted for the hypothetical basic-helix-loop-helix structure. Virology 182, 84-93.
Kao, M. C.,Law, S. L., Chuang, T. C. and Lin, Y. S. (1998) In vitro gene transfer in mammalian cells via a new cationic liposome formulation. Oncology report 5, 625-629.
Kameda, T., Yasui, W., Yoshida, K., Tsujino, T., Nakyama, H., Ito, M., Ito, H. & Tahara, E. (1990). Expression of ERBB2 in human gastric carcinomas: Relationship between p185ERBB2 expression and the gene amplification. Cancer Res. 50, 8002-8009.
Kern, J. A., Schwartz, D. A., Nordberg, J. E., Weiner, D. B., Green, M. t., Torney, I. & Robinson, R. A. (1990) p185neu expression in human lung adenocarcinomas predicts shortened survial. Cancer Res. 50, 5184-5191.
Kita, Y. A. Barff, J., Luo, Y., Wen, D., Brankow, D., Hu, S., Liu, N., Prigent, S. A., Gullick, W. J. & Nicolson, M. (1994) NDF/heregulin stimulates the phosphorylation of HER3/erbB-3. FEBS 349, 139-143.
Lee, K. F., Simon, H., Chen, H., Bastes, B., Hung, M. C. & Hauser, C. (1995) Reguirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 378, 394-398.
Lemmon, M. A. and Schlessinger J. (1994) Regulation of signal transduction and signal diversity by receptor oligomerzation. TIBS 19, 459-463.
Liu, G. Y.: Transcriptional repression of the neu oncogene by two peptides derived from the SV40 large T antigen. Master thesis (adviser: Kao, M. C. ), National Defense Medical Center, Taipei, Taiwan, 1995.
Lin, C. S., Chen, J. Y., Yang, C. S.and Wang, W. B. (1999) Epstein-Barr virus EBNA-2 retard cell growth by post-translational modification of p53 and induction of p21WAF1. Second NHRI Conference on Tumor Associated Herpesviruses. Program and Abstracts. p32.
Mackey, D., Middleton, T. and Sugden, B. (1995) Multiple regions within EBNA1 can link DNAs. J. Virol 69, 6199-6208.
Marchionni, M. A., Goodeari, A. D. J., Chen, M. S., Bermingham-Mc Donogh, O., Sudhalter, J., Kobayashi, K., Wroblewski, D., Lynch, C., Baldassare, M., Hiles, I., Davis, J. B., Hsuan, J. J., Totty, N. F., Otsu, M., McBurney, R. N., Waterfield, M. D., Stroobant, P. & Gwynne, D. (1993) Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature 362, 312-318.
Marchionni, M. A. (1995) neu tack on neuregulin. Nature 378, 334-335.
Matin, A. & Hung, M. C. (1993) Negative regulation of the neu promoter by the SV40 large T antigen. Cell Growth Differ. 4, 1-6.
Matin, A. & Hung, M. C. (1994) The retinoblastoma gene products, Rb, represses neu expression through two regions within the neu regulatory sequence. Oncogene 9, 1333-1339.
Matin, A., Xie, Y., Kao, M. C. & Hunag, M. C. (1995) Rodent p53 suppersses the transforming activity of the activated neu oncogene by modulating the basal promoter activity of neu. International J. Oncol. 6, 1087-1092.
Mizuguchi, G., Kanei-Ishii, C., Tokahashi, T., Yasulawa, T., Nagase, T., Horikoshi, N., Yamamoto, T. & Ishii, S. (1995) c-Myb repression of c-erbB2 Trans cription by direct binding to the c-erbB2 promoter. J. Biol. Chem. 270, 9384-9389.
Molina, H., Brenner, C., Jacobi, S., Gorka, J., Carel, J. C., Kinoshita, T. and Holers, V. M.(1991) Analysis of Epstein-Barr virus-binding sites on complement receptor 2 (CR2/CD2)using human-mousr chimeras and peptides. At least two distinct sites are necessary for ligand-receptor interaction. J. Biol. Chem. 266, 12173-12179.
Muss, H. B., Thor, A. D., Berry, D. A., Kute, T., Liu, E.T., Koerner, F., Cirrincione, C. T., Budman, D. R., Wood, W. C., Barcos, M. and Henderson, I. C. (1994) N. Engl. J. Med. 330, 1260-1266.
Noonberg, S. B., Scott, G. K., Hunt, C. A., Hogan, M. E. & Benz, C. C. (1994) Inhibition of transcription factor binding to the HER2 promoter by triple-forming oligodeoxyribonucleotides. Gene 149, 123-126.
Palowman, G. D., Green, J. M., Culouscou, J. M., Cariton, G. W., Rothwell, V. M. & Buckiey, S. (1993) Heregulin induces tyrosine phosphorylation of HER4/p180erbB4 . Nature 366, 473-475.
Park, J. W., Hong, K., Carter, P., Asgari, H., Guo, L. Y., Keller, G. A., Wirth, C., Shalaby, R., Kotts, C., Wood, W. I., Parahadjopulos, D. & Benz, C. C. (1995) Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc. Natl. Acad. Sci. USA 92, 1327-1331.
Pietras, R. J., Fendly, B. M., Chazin, V. R., Pegram, M. D., Howell, S. B. And Slamon, D. J. (1994) oncogene 9, 1829-1838.
Polvino-Bodnar, M. and Schaffer, P. A. (1992) DNA binding activity is required for EBNA1-depwndent transcripation activation and DNA replication. Virology 187, 591-603.
Qian, X., Levea, C. M., Freeman, J. K., Dougall, W. C. & Greene, M. I. (1994) Heterodimerization of epidermal growth factor receptor and wild-type or kinase-deficient Neu: a mechanism of interreceptor kianse activation and transphosphorylation. Proc. Natl. Acad. Sci. USA 91, 1500-1504.
Rawlins, D. R., Milman, G., Hayward, S. D. and Hayward, G. S. (1985) Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA1) to clustered site in the plasmid maintenance region. Cell. 42, 859-868.
Reedman, B. M. and Klein, G. (1973) Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell line. Int. J Cancer 11, 499-520.
Rowe, D. T., Evan, G. I., Wallace, L.E., Farrell, P. J. and Rickinson, A. B. (1986) Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt''s lymphoma cells. EMBO J 5, 2599-2607
Salmons, B. & Gunzburg, W. H. (1993) Targeting of retroviral vectors for gene therapy. Human Gene Therapy 4, 129-141.
Salmon, D. J.,Clark, G. M., Wong, S. G., Levin, W. J., Ullrch, A. And McGuir, W. L. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science 235, 177-182.
Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A., wong, S. G., Keith D. E., Levin, W. J., Stuart, S. G., Udove, J., Ullrich, A. And Press, M. F. (1989) Studies of the HER2/neu proto-oncogene in human breast and ovarian cancer. Science 244, 707-712.
Samanta, A., Levea, C. M., Dougall, W. C., Qian, X. & Greene, M. I. (1994) Ligand and p185c-neu density govern receptor interactions and tyrosine kinase activation. Proc. Natl. Acad. Sci. USA 91, 1711-1715.
Sample, J., Brooks, L., Sample, C., Yoing, L., Rowe, M., Gregory, C., Rickinson, A. and Kieff, E. (1991)Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr nuclear antigen 1 transcriptional initiation site. Proc. Natl Acad. Sci. USA 88, 6343-6347.
Sample, J., Daniel Henson, E. B. and Sample, C. (1992)The Epstein-Barr virus nuclear protein 1 promoter active in type I latency is autoregulated. J. Virol 66, 4654-4661.
Schaefer, B., Woisetschlaeger, M., Strominger, J. and Speck, S.(1991)Exclusive expression of Epstein-Barr virus nuclear antigen 1 in Burkitt lymphoma arises from a third promoter, distinct from the promoters used in latently infected lymphocytes. Proc. Natl Acad. Sci. USA 88, 6550-6561.
Schneider, P. M., Hung, M. C. Chiocca, S. M., Manning, J., Zhao, X., Fang, K. & Roth, J. A. (1989) Differential expression of the c-erbB-2 gene in human small cell and non-small cell lung cancer Cancer Res. 49, 4968-4971.
Shepard, H. M., Lewis, G. D., Sarup, J. C. (1992) Monoclonal antibody therapy of human cancer: taking the HER-2 protooncogene to the clinic. J Clin Immunol 11, 117-127
Sliwlowski, M. X., Schaefer, G., Alita, R. W., Lofgren, J. A., Fitzpatrick, V. D., Nuijens A., Fendly, B. M., Cerione, R. A., Vandlen, R. L. & Csrraway, K. L. (1994) Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for Heregulin. J. Biol. Chem. 269, 14661-14665.
Snudden, D. K., Hearing, J., Smith, P. R., Grasser, F. A. and Griffin, B. E. (1994) EBNA1, the major nuclear antigen of Epstein-Barr virus, resembles ''RGG'' RNA bindimg protein.EMBO.13, 4840-4847.
Smith, P. R. and Griffin, B. E.(1992)J. Virol. 66, 706-714.
Suen, T. C. & Hung, M. C. (1990) Multiple cis- and trans-acting elements involved in regulation of the neu gene. Mol. Cell. Biol. 10, 6306-6315.
Suen, T. C. & Hung, M. C. (1991) c-Myc reverses neu-induced transformed morphology by transcriptional repression. Mol. Cell. Biol. 11, 354-362.
Tan, M., Yao, J. and Yu, d. (1997) Overexpression of the c-erbB2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities.Cancer Res 57, 1199-1205.
Ueki, N., Oda, T., Kondo, M., Yano, K., Noguchi, T. and Muramatsu, M. (1998) Selection system for genes encoding nuclear-targeting proteins. Nature Biotechnology 16, 1338-1342.
Ueno, N. T., Yu, D. and Hung, M. C. (1997)Chemosensitization of HER-2/neu-overexpressing human breast cancer cell to paclitaxel(Taxol)by adenovirus type 5 E1A. oncogene 15, 953-960.
Wen, D., Peles, E., Cupples, R., Suggs, S. V., Bacus, S. S., Luo, Y., Trail, G., Hu, S., Silbiger, S. M., Levy, R. B., Koski, R. A., Lu, H. S. & Yarden, Y. (1992) Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and immunoglobulin homology unit. Cell 69, 559-572.
Williams, T. M., Weiner, D. W., Greene, M. I. and Maguire, H. C., Jr. (1991) Pathobiology 59, 46-52.
Xie, Y. & Hung, M. C. (1994) Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation. Biochem. Biophys. Res. Commun. 203, 1589-1598.
Yamamoto, T., Ikawa, S., akiyama, T., Semba, K., Nomura, N., Miyajima, N., Saito, T. & Toyoshima K. (1986) Similarity of protein encoded by the human c-erbB2 gene to epidermal growth factor receptor. Nature 319, 230-234.
Yates, J., Warren, N., Reisman, D. and Sugden, B. (1984) A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc. Natl. Acad. Sci. USA. 81, 3806-10.
Yu, D. and Hung M. C. (1991) Expression of activated rat neu oncogene is sufficient to induce experimental metastasis in 3T3 cells. Oncogene 6, 1191-1196
Yu, D. and Hung M. C. (1995) Molecular basis of oncology-chpater 5: The HER-2/neu gene in human cancer. Blackwell Science, 131-162.
Yu, D., Jing, T., Lin, B., Yao, J.,Tan, M., Mcdonnell, T.J. and Hung, M.C. (1998) Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21cip1, which inhibits p34cdc2 kinase. Molecular Cell 2, 581-591
Yu, D., Liu, B., Tan, M., Li, J., Wang, S-S and Hung, M. C. (1996) Overexpression of c-erbB-2/neu in braest cancer cels confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene 13, 1359-1365.
Yu, D., Matin, A., Hinds, P. W., and Hung, M.C. (1994) Transcriptional regulation of neu by RB and E1A in Rat-1 cells. Cell Growth & Differentition., 5, 431-438.
Yu, D., Suen, T. C., Yan, D. H., Chang, L. S. & Hung, M. C. (1990) Transcriptional repression of the neu protooncogene by the adenovirus 5 E1A gene products. Proc. Natl. Acad. Sci. USA 87, 4499-4503.
Zhang, K., Sun, J., Liu, N., Wen, D., Chang, D., Thomason, A. & Yoshinaga, S. K. (1996) Transformation of NIH3T3 cells by HER3 or HER4 Recepfors Requires the Presence of HER1 or HER2. J. Biol. Chem. 271, 3884-3890.
Zhang, L., Chang, C. J., Bacus, S. S. & Hung, M.C. (1995) Suppressed transformation and differentiation of HER-2/neu-overexpressing breast cancer cells by emodin. Cancer Res. 55, 3890-3896.
莊子超 (1996) 國防醫學院生物化學研究所碩士論文:發展一新微脂粒基因傳送系統及猿病毒突變型腫瘤抗原抑制 neu 致癌基因表現之分析。
魏宗德 (1997) 國防醫學院生物化學研究所碩士論文:非洲淋巴細胞瘤病毒胞核抗原-1 抑制致癌基因 HER-2/neu 之轉錄表現。
李瓔祝 (1998) 國防醫學院生物化學研究所碩士論文:探討 EB 病毒核抗原-1 抑制神經膠原致癌基因表現的順式作用序列。
胡誌麟( 1998) 國防醫學院生物化學研究所碩士論文:非洲淋巴細胞瘤病毒胞核抗原-1 氮端八十六個胺酸區域可為神經膠原致癌基因的轉形抑制劑。
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top