(3.80.6.131) 您好!臺灣時間:2021/05/14 03:40
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:林鉦展
研究生(外文):Cheng-Chan
論文名稱:探討EGCG對人類乳癌細胞株MCF-7中Heregulin-β1訊息傳遞路徑的影響
論文名稱(外文):Study on the effects of EGCG on heregulin-β1-mediated signaling in human breast cancer cell line MCF-7
指導教授:陳威仁陳威仁引用關係
指導教授(外文):Wei-Jen Chen
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:生物醫學科學學系碩士班
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:2008
畢業學年度:96
語文別:中文
論文頁數:78
相關次數:
  • 被引用被引用:0
  • 點閱點閱:106
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
腫瘤相關的脂肪酸合成酶(Tumor-associated fatty acid synthase, FASN)的表現在乳癌發生的狀況下,往往與生長因子接受器(Growth factor receptor)的高量表現有關,例如:EGFR(Epidermal growth factor receptor)或是erbB2接受器;而有30%的乳癌患者有erbB2接受器或是它的Trans-ligand,Heregulin(HRG)過量表現的情況;而由上述可以推測:erbB2接受器引發FASN的表現對乳癌發生的進程而言是必需的。
在之前的研究中,在人類乳癌細胞株MCF-7,用綠茶多酚 (-)-Epigallocatechin-3-gallate(EGCG),透過抑制PI3K/Akt路徑,造成由EGF引發FASN的表現量下降;這也許提示了,EGCG可以降低由erbB2接受器引發FASN的可能性。
在本文中,我們假設EGCG可以抑制由erbB2接受器所引發FASN的表量,且具有降低乳癌細胞增生的能力;所以我們以erbB3接受器的Natural ligand,HRG-β1,刺激MCF-7細胞株,來引發erbB2接受器的活化;我們觀察到HRG-β1可以引發FASN的表現;以加入轉錄抑制劑,Antinomycin D(Act D)與轉譯抑制劑,Cycloheximide(CHX)進行研究,證實了因HRG-β1的影響而引發FASN的表現,其影響點在於轉錄階段(Transcriptional level)。之後為解HRG-β1引發的訊息傳遞路徑是如何提高FASN的表現,所以用專一性的蛋白激酶抑制劑與Dominant-negative的方法,證實HRG-β1是透過PI3K/Akt路徑與MEK/ERK1/2路徑,引發FASN的表現。我們也發現HRG-β1可以引發erbB2接受器與erbB3接受器可以形成Heterodimer,之後促使FASN的表現。
另一方面,EGCG具有降低由HRG-β1所引發FASN表現量的能力,是透過降低Akt如ERK1/2的活性,干擾erbB2接受器與erbB3接受器的偶合與活化,達到效果;這說明了EGCG在乳癌的癌症化學預防上的角色。
總而言之,我們的研究證實了在MCF-7乳癌細胞株中,EGCG抑制了由HRG-β1所引發的erbB2與erbB3接受器的Heterodimer,結果降低了MEK/ERK1/2路徑與PI3K/Akt路徑的功能,包括了細胞的生長與存活。

Tumor-associated fatty acid synthase (FASN) has been linked to breast cancer carcinogenesis and can be up-regulated by growth factor receptor such as epidermal growth factor receptor (EGFR) and erbB2. About 30% of breast cancer patients bearing overexpressed erbB2 receptor or its trans-ligand heregulin (HRG) are poor prognosis, suggesting that erbB2-mediated FAS induction may be essential for breast cancer progression. In fact, our previous study shows that green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) could suppress EGF-induced FASN expression in human breast cancer cell line MCF-7 via inhibiting PI3K/Akt pathway, raising the possibility whether EGCG also reduces erb2-mediated FASN expression similar to our previous data as described above.
In this study, we hypothesize that EGCG could inhibit erb2-mediated FASN expression and then down-regulate breast cancer cell proliferation. To this end, we used the HRG-β1, a natural ligand of erbB3 which can transactivate erbB2, to stimualte MCF-7 breast cancer cells. We found that HRG-β1 increased FASN expression and this increment of FASN expression could be reduced by the addition of transcriptional inhibitor, antinomycin D (Act D) and translational inhibitor, cycloheximide (CHX), respectively, suggesting that HRG-β1 induces FASN expression at a transcriptional level. Exploring the HRG-β1-mediated signaling pathways involving in FASN induction by specific protein kinase inhibitors and dominant-negative method, we found that PI3K/Akt pathway and MEK/ERK1/2 pathway are essential for the expression of FASN regulated by HRG-β1. We also found that erbB2-erbB3 heterodimerization by HRG-β1 can regulates FASN up-regulation.
On the other hand, tea polypolyphenol EGCG strongly inhibited HRG-β1-triggered FASN expression and proliferation by down-regulating ERK1/2 activation, Akt activation and coordination of erbB2 and erbB3, respectively, exhibiting an vital role of EGCG on breast cancer chemoprevention.
To sum up, our current study demonstrated that EGCG inhibited HRG-β1-stimulated heterodimerization of erbB2 and erbB3 in MCF-7 cells, and consequently down-regulated the downstream signals including MEK/ERK1/2 pathway and PI3K/Akt pathway whose functions are essential for cell growth and survival.

壹、中文摘要 4
Abstract 6
參、序論 8
3-1、表皮生長因子接受器家族(Epidermal Growth factor receptor family, EGFR family)8
3-2、MAPK路徑與Akt路徑的訊息傳遞 13
3-3、脂肪酸合成酶(Fatty acid synthase, FAS)18
3-4、EGCG((-)-Epigallocatechin-3-gallate)19
3-5、實驗動機 21
肆、材料與方法 22
4-1、細胞培養 22
4-2、基因的轉染作用(Transfection) 25
4-3、細胞存活率分析 25
4-4、免疫沉澱(Immuno-precipitation)與西方點墨法(Western Blotting) 27
4-5、反轉錄-聚合酶鏈鎖反應(Reverse transcription - polyermerase chain reaction, RT-PCR) 33
伍、結果 38
5-1、在MCF-7細胞株中,由HRG-β1所引發的FASN表現,HRG-β1的影響的位置在轉錄,而非轉譯 38
5-2、在MCF-7細胞株中,EGCG抑制由HRG-β1引發的MAPK路徑與Akt路徑,導致FASN的表現量下降 39
5-3、EGCG可以抑制由HRG-β1所引發的erbB2接受器與erbB3接受器的偶合與磷酸化現象 40
5-4、EGCG可以抑制由HRG-β1所引發的細胞增生 42
陸、討論 44
柒、參考文獻 49
捌、附圖 66
圖一、在MCF-7細胞株中,HRG-β1可以引發FASN蛋白質的表現 66
圖二、Antinomycin D與Cycloheximide抑制HRG-β1所引發的FASN基因表現 67
圖三、HRG-β1引發FASN的表現需要ERK1/2與Akt的活化 68
圖四、證實EGCG會抑制由HRG-β1所引發的FASN表現 69
圖五、EGCG會抑制由HRG-β1所引發的ERK1/2與Akt的活化 70
圖六、以抑制劑來證明,HRG-β1所引發FASN的表現是經由erbB2接受器,而非EGFR 71
圖七、HRG-β1所引發的erbB2接受器與erbB3接受器的磷酸化會被EGCG所抑制 72
圖八、HRG-β1所引發的erbB2接受器與erbB3接受器的偶合會被EGCG所干擾 73
圖九、EGCG可以減低由HRG-β1所引發的細胞增生現象 74
玖、附錄 75

Alimandi, M., A. Romano, M. C. Curia, R. Muraro, P. Fedi, S. A. Aaronson, P. P. Di Fiore and M. H. Kraus (1995). "Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas." Oncogene 10(9): 1813-21.

Alo, P. L., P. Visca, G. Trombetta, A. Mangoni, L. Lenti, S. Monaco, C. Botti, D. E. Serpieri and U. Di Tondo (1999). "Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas." Tumori 85(1): 35-40.

Andrechek, E. R. and W. J. Muller (2000). "Tyrosine kinase signalling in breast cancer: tyrosine kinase-mediated signal transduction in transgenic mouse models of human breast cancer." Breast Cancer Res 2(3): 211-6.

Andrulis, I. L., S. B. Bull, M. E. Blackstein, D. Sutherland, C. Mak, S. Sidlofsky, K. P. Pritzker, R. W. Hartwick, W. Hanna, L. Lickley, R. Wilkinson, A. Qizilbash, U. Ambus, M. Lipa, H. Weizel, A. Katz, M. Baida, S. Mariz, G. Stoik, P. Dacamara, D. Strongitharm, W. Geddie and D. McCready (1998). "neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group." J Clin Oncol 16(4): 1340-9.

Badra, F. A., M. V. Karamouzis, P. Ravazoula, E. Likaki-Karatza, E. Tzorakoleftherakis, D. Koukouras, G. Iconomou, N. Xiros, D. Siablis, A. G. Papavassiliou and H. P. Kalofonos (2006). "Non-palpable breast carcinomas: correlation of mammographically detected malignant-appearing microcalcifications and epidermal growth factor receptor (EGFR) family expression." Cancer Lett 244(1): 34-41.

Barnes, N. L., S. Khavari, G. P. Boland, A. Cramer, W. F. Knox and N. J. Bundred (2005). "Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast." Clin Cancer Res 11(6): 2163-8.

Basu, S., N. F. Totty, M. S. Irwin, M. Sudol and J. Downward (2003). "Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis." Mol Cell 11(1): 11-23.

Benz, C. C., G. K. Scott, J. C. Sarup, R. M. Johnson, D. Tripathy, E. Coronado, H. M. Shepard and C. K. Osborne (1992). "Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu." Breast Cancer Res Treat 24(2): 85-95.

Benzel, I., A. Bansal, B. L. Browning, N. W. Galwey, P. R. Maycox, R. McGinnis, D. Smart, D. St Clair, P. Yates and I. Purvis (2007). "Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia." Behav Brain Funct 3: 31.

Blank, S. V., R. Chang and F. Muggia (2005). "Epidermal growth factor receptor inhibitors for the treatment of epithelial ovarian cancer." Oncology (Williston Park) 19(4): 553-9; discussion 560-2, 567.

Bodey, B., B. Bodey, Jr., A. M. Groger, J. V. Luck, S. E. Siegel, C. R. Taylor and H. E. Kaiser (1997). "Clinical and prognostic significance of the expression of the c-erbB-2 and c-erbB-3 oncoproteins in primary and metastatic malignant melanomas and breast carcinomas." Anticancer Res 17(2B): 1319-30.

Bos, J. L. (1989). "ras oncogenes in human cancer: a review." Cancer Res 49(17): 4682-9.

Brazil, D. P., Z. Z. Yang and B. A. Hemmings (2004). "Advances in protein kinase B signalling: AKTion on multiple fronts." Trends Biochem Sci 29(5): 233-42.
Breuleux, M. (2007). "Role of heregulin in human cancer." Cell Mol Life Sci 64(18): 2358-77.

Cantley, L. C. (2002). "The phosphoinositide 3-kinase pathway." Science 296(5573): 1655-7.

Citri, A. and Y. Yarden (2006). "EGF-ERBB signalling: towards the systems level." Nat Rev Mol Cell Biol 7(7): 505-16.

Cohen, R. B. (2003). "Epidermal growth factor receptor as a therapeutic target in colorectal cancer." Clin Colorectal Cancer 2(4): 246-51.

Dent, P., A. Yacoub, P. B. Fisher, M. P. Hagan and S. Grant (2003). "MAPK pathways in radiation responses." Oncogene 22(37): 5885-96.

Diermeier, S., G. Horvath, R. Knuechel-Clarke, F. Hofstaedter, J. Szollosi and G. Brockhoff (2005). "Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation." Exp Cell Res 304(2): 604-19.

Fleischmann, M. and P. B. Iynedjian (2000). "Regulation of sterol regulatory-element binding protein 1 gene expression in liver: role of insulin and protein kinase B/cAkt." Biochem J 349(Pt 1): 13-7.

Fontanini, G., M. De Laurentiis, S. Vignati, S. Chine, M. Lucchi, V. Silvestri, A. Mussi, S. De Placido, G. Tortora, A. R. Bianco, W. Gullick, C. A. Angeletti, G. Bevilacqua and F. Ciardiello (1998). "Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival." Clin Cancer Res 4(1): 241-9.

Friess, H., L. Wang, Z. Zhu, R. Gerber, M. Schroder, A. Fukuda, A. Zimmermann, M. Korc and M. W. Buchler (1999). "Growth factor receptors are differentially expressed in cancers of the papilla of vater and pancreas." Ann Surg 230(6): 767-74; discussion 774-5.

Garrett, T. P., N. M. McKern, M. Lou, T. C. Elleman, T. E. Adams, G. O. Lovrecz, M. Kofler, R. N. Jorissen, E. C. Nice, A. W. Burgess and C. W. Ward (2003). "The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors." Mol Cell 11(2): 495-505.

Ghetie, V., K. Nilsson and J. Sjoquist (1974). "Identification of cell surface immunoglobulin markers by protein A-containing fluorescent staphylococci." Scand J Immunol 3(4): 397-403.

Graus-Porta, D., R. R. Beerli, J. M. Daly and N. E. Hynes (1997). "ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling." Embo J 16(7): 1647-55.

Guy, P. M., J. V. Platko, L. C. Cantley, R. A. Cerione and K. L. Carraway, 3rd (1994). "Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity." Proc Natl Acad Sci U S A 91(17): 8132-6.

Hederstedt, L. and L. Rutberg (1981). "Succinate dehydrogenase--a comparative review." Microbiol Rev 45(4): 542-55.

Herbst, R. S. (2004). "Review of epidermal growth factor receptor biology." Int J Radiat Oncol Biol Phys 59(2 Suppl): 21-6.

Holmes, W. E., M. X. Sliwkowski, R. W. Akita, W. J. Henzel, J. Lee, J. W. Park, D. Yansura, N. Abadi, H. Raab, G. D. Lewis and et al. (1992). "Identification of heregulin, a specific activator of p185erbB2." Science 256(5060): 1205-10.

Huang, H. J., P. Neven, M. Drijkoningen, R. Paridaens, H. Wildiers, E. Van Limbergen, P. Berteloot, F. Amant, I. Vergote and M. R. Christiaens (2005). "Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer." J Clin Pathol 58(6): 611-6.

Hudziak, R. M., G. D. Lewis, M. Winget, B. M. Fendly, H. M. Shepard and A. Ullrich (1989). "p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor." Mol Cell Biol 9(3): 1165-72.

Huh, S. W., S. M. Bae, Y. W. Kim, J. M. Lee, S. E. Namkoong, I. P. Lee, S. H. Kim, C. K. Kim and W. S. Ahn (2004). "Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines." Gynecol Oncol 94(3): 760-8.

Iwamoto, R. and E. Mekada (2006). "ErbB and HB-EGF signaling in heart development and function." Cell Struct Funct 31(1): 1-14.

Jakobovits, A. (2008). "Monoclonal antibody therapy for prostate cancer." Handb Exp Pharmacol(181): 237-56.

Karamouzis, M. V., F. A. Badra and A. G. Papavassiliou (2007). "Breast cancer: the upgraded role of HER-3 and HER-4." Int J Biochem Cell Biol 39(5): 851-6.

Kawano, O., H. Sasaki, K. Endo, E. Suzuki, H. Haneda, H. Yukiue, Y. Kobayashi, M. Yano and Y. Fujii (2007). "ErbB3 mRNA Expression Correlated with Specific Clinicopathologic Features of Japanese Lung Cancers." J Surg Res.

Kersemaekers, A. M., G. J. Fleuren, G. G. Kenter, L. J. Van den Broek, S. M. Uljee, J. Hermans and M. J. Van de Vijver (1999). "Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis." Clin Cancer Res 5(3): 577-86.

Khan, N., F. Afaq, M. Saleem, N. Ahmad and H. Mukhtar (2006). "Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate." Cancer Res 66(5): 2500-5.

Kolch, W. (2005). "Coordinating ERK/MAPK signalling through scaffolds and inhibitors." Nat Rev Mol Cell Biol 6(11): 827-37.

Kuhajda, F. P. (2000). "Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology." Nutrition 16(3): 202-8.

Kumar, N., D. Shibata, J. Helm, D. Coppola and M. Malafa (2007). "Green tea polyphenols in the prevention of colon cancer." Front Biosci 12: 2309-15.

Kumar-Sinha, C., K. W. Ignatoski, M. E. Lippman, S. P. Ethier and A. M. Chinnaiyan (2003). "Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis." Cancer Res 63(1): 132-9.

Kurebayashi, J. (2001). "Biological and clinical significance of HER2 overexpression in breast cancer." Breast Cancer 8(1): 45-51.

Kyriakis, J. M. and J. Avruch (2001). "Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation." Physiol Rev 81(2): 807-69.

Lambert, J. D. and C. S. Yang (2003). "Mechanisms of cancer prevention by tea constituents." J Nutr 133(10): 3262S-3267S.

Le, X. F., C. R. Varela and R. C. Bast, Jr. (2002). "Heregulin-induced apoptosis." Apoptosis 7(6): 483-91.

Lemoine, N. R., D. M. Barnes, D. P. Hollywood, C. M. Hughes, P. Smith, E. Dublin, S. A. Prigent, W. J. Gullick and H. C. Hurst (1992). "Expression of the ERBB3 gene product in breast cancer." Br J Cancer 66(6): 1116-21.

Levy, D., Y. Adamovich, N. Reuven and Y. Shaul (2007). "The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73." Cell Death Differ 14(4): 743-51.

Lewis, G. D., I. Figari, B. Fendly, W. L. Wong, P. Carter, C. Gorman and H. M. Shepard (1993). "Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies." Cancer Immunol Immunother 37(4): 255-63.

Lin, J. D. and T. C. Chao (2005). "Vascular endothelial growth factor in thyroid cancers." Cancer Biother Radiopharm 20(6): 648-61.

Liu, Y., Y. M. Tao, R. S. Woo, W. C. Xiong and L. Mei (2007). "Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons." Biochem Biophys Res Commun 354(2): 505-10.

Lu, S. and M. C. Archer (2005). "Fatty acid synthase is a potential molecular target for the chemoprevention of breast cancer." Carcinogenesis 26(1): 153-7.

Menendez, J. A. and R. Lupu (2007). "Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis." Nat Rev Cancer 7(10): 763-77.

Menendez, J. A., L. Vellon, I. Mehmi, B. P. Oza, S. Ropero, R. Colomer and R. Lupu (2004). "Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells." Proc Natl Acad Sci U S A 101(29): 10715-20.

Milgraum, L. Z., L. A. Witters, G. R. Pasternack and F. P. Kuhajda (1997). "Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma." Clin Cancer Res 3(11): 2115-20.

Moulder, S. L., F. M. Yakes, S. K. Muthuswamy, R. Bianco, J. F. Simpson and C. L. Arteaga (2001). "Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo." Cancer Res 61(24): 8887-95.

Nam, S., D. M. Smith and Q. P. Dou (2001). "Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo." J Biol Chem 276(16): 13322-30.

Naresh, A., W. Long, G. A. Vidal, W. C. Wimley, L. Marrero, C. I. Sartor, S. Tovey, T. G. Cooke, J. M. Bartlett and F. E. Jones (2006). "The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells." Cancer Res 66(12): 6412-20.

Navolanic, P. M., L. S. Steelman and J. A. McCubrey (2003). "EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (Review)." Int J Oncol 22(2): 237-52.

Noonberg, S. B. and C. C. Benz (2000). "Tyrosine kinase inhibitors targeted to the epidermal growth factor receptor subfamily: role as anticancer agents." Drugs 59(4): 753-67.

Olayioye, M. A. (2001). "Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members." Breast Cancer Res 3(6): 385-9.

Olayioye, M. A., R. M. Neve, H. A. Lane and N. E. Hynes (2000). "The ErbB signaling network: receptor heterodimerization in development and cancer." Embo J 19(13): 3159-67.

Ono, K. and J. Han (2000). "The p38 signal transduction pathway: activation and function." Cell Signal 12(1): 1-13.

Papageorgio, C. and M. C. Perry (2007). "Epidermal growth factor receptor-targeted therapy for pancreatic cancer." Cancer Invest 25(7): 647-57.

Pearson, G., F. Robinson, T. Beers Gibson, B. E. Xu, M. Karandikar, K. Berman and M. H. Cobb (2001). "Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions." Endocr Rev 22(2): 153-83.

Pinkas-Kramarski, R., L. Soussan, H. Waterman, G. Levkowitz, I. Alroy, L. Klapper, S. Lavi, R. Seger, B. J. Ratzkin, M. Sela and Y. Yarden (1996). "Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions." Embo J 15(10): 2452-67.

Pornchai, O.-c., P. H. Rhys-Evans, H. Modjtahedi and S. A. Eccles (2002). "The role of c-erbB receptors and ligands in head and neck squamous cell carcinoma." Oral Oncol 38(7): 627-40.

Rajkumar, T., G. W. Stamp, H. S. Pandha, J. Waxman and W. J. Gullick (1996). "Expression of the type 1 tyrosine kinase growth factor receptors EGF receptor, c-erbB2 and c-erbB3 in bladder cancer." J Pathol 179(4): 381-5.

Rashid, A., E. S. Pizer, M. Moga, L. Z. Milgraum, M. Zahurak, G. R. Pasternack, F. P. Kuhajda and S. R. Hamilton (1997). "Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia." Am J Pathol 150(1): 201-8.

Roskoski, R., Jr. (2004). "The ErbB/HER receptor protein-tyrosine kinases and cancer." Biochem Biophys Res Commun 319(1): 1-11.

Rossi, S., E. Graner, P. Febbo, L. Weinstein, N. Bhattacharya, T. Onody, G. Bubley, S. Balk and M. Loda (2003). "Fatty acid synthase expression defines distinct molecular signatures in prostate cancer." Mol Cancer Res 1(10): 707-15.

Roux, P. P. and J. Blenis (2004). "ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions." Microbiol Mol Biol Rev 68(2): 320-44.

Roy, K., J. C. Murtie, B. F. El-Khodor, N. Edgar, S. P. Sardi, B. M. Hooks, M. Benoit-Marand, C. Chen, H. Moore, P. O''Donnell, D. Brunner and G. Corfas (2007). "Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders." Proc Natl Acad Sci U S A 104(19): 8131-6.

Sah, J. F., S. Balasubramanian, R. L. Eckert and E. A. Rorke (2004). "Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases." J Biol Chem 279(13): 12755-62.

Schlessinger, J. (2000). "Cell signaling by receptor tyrosine kinases." Cell 103(2): 211-25.

Shankar, S., S. Ganapathy and R. K. Srivastava (2007). "Green tea polyphenols: biology and therapeutic implications in cancer." Front Biosci 12: 4881-99.

Shimizu, M., A. Deguchi, J. T. Lim, H. Moriwaki, L. Kopelovich and I. B. Weinstein (2005). "(-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells." Clin Cancer Res 11(7): 2735-46.

Slamon, D. J., G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich and W. L. McGuire (1987). "Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene." Science 235(4785): 177-82.

Slamon, D. J., W. Godolphin, L. A. Jones, J. A. Holt, S. G. Wong, D. E. Keith, W. J. Levin, S. G. Stuart, J. Udove, A. Ullrich and et al. (1989). "Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer." Science 244(4905): 707-12.

Slamon, D. J., B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde, T. Fleming, W. Eiermann, J. Wolter, M. Pegram, J. Baselga and L. Norton (2001). "Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2." N Engl J Med 344(11): 783-92.

Song, G., G. Ouyang and S. Bao (2005). "The activation of Akt/PKB signaling pathway and cell survival." J Cell Mol Med 9(1): 59-71.

Swinnen, J. V., T. Roskams, S. Joniau, H. Van Poppel, R. Oyen, L. Baert, W. Heyns and G. Verhoeven (2002). "Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer." Int J Cancer 98(1): 19-22.

Swinnen, J. V., P. P. Van Veldhoven, L. Timmermans, E. De Schrijver, K. Brusselmans, F. Vanderhoydonc, T. Van de Sande, H. Heemers, W. Heyns and G. Verhoeven (2003). "Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains." Biochem Biophys Res Commun 302(4): 898-903.

Syed, D. N., F. Afaq, M. H. Kweon, N. Hadi, N. Bhatia, V. S. Spiegelman and H. Mukhtar (2007). "Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-kappaB activation in normal human bronchial epithelial cells." Oncogene 26(5): 673-82.

Szutowicz, A., J. Kwiatkowski and S. Angielski (1979). "Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast." Br J Cancer 39(6): 681-7.

Tzahar, E., H. Waterman, X. Chen, G. Levkowitz, D. Karunagaran, S. Lavi, B. J. Ratzkin and Y. Yarden (1996). "A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor." Mol Cell Biol 16(10): 5276-87.

Umeda, D., S. Yano, K. Yamada and H. Tachibana (2007). "Green tea polyphenol epigallocatechin-3-gallate (EGCG) signaling pathway through 67-kDa laminin receptor." J Biol Chem 283(6):3050-8.

Vanden Bempt, I., M. Drijkoningen and C. De Wolf-Peeters (2007). "The complexity of genotypic alterations underlying HER2-positive breast cancer: an explanation for its clinical heterogeneity." Curr Opin Oncol 19(6): 552-7.

Vivanco, I. and C. L. Sawyers (2002). "The phosphatidylinositol 3-Kinase AKT pathway in human cancer." Nat Rev Cancer 2(7): 489-501.

Wells, A. and J. R. Grandis (2003). "Phospholipase C-gamma1 in tumor progression." Clin Exp Metastasis 20(4): 285-90.

Widmann, C., P. Gerwins, N. L. Johnson, M. B. Jarpe and G. L. Johnson (1998). "MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis." Mol Cell Biol 18(4): 2416-29.

Widmann, C., N. L. Johnson, A. M. Gardner, R. J. Smith and G. L. Johnson (1997). "Potentiation of apoptosis by low dose stress stimuli in cells expressing activated MEK kinase 1." Oncogene 15(20): 2439-47.

Woodgett, J. R. (2005). "Recent advances in the protein kinase B signaling pathway." Curr Opin Cell Biol 17(2): 150-7.

Yeh, C. W., W. J. Chen, C. T. Chiang, S. Y. Lin-Shiau and J. K. Lin (2003). "Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects." Pharmacogenomics J 3(5): 267-76.

Yi, E. S., D. Harclerode, M. Gondo, M. Stephenson, R. W. Brown, M. Younes and P. T. Cagle (1997). "High c-erbB-3 protein expression is associated with shorter survival in advanced non-small cell lung carcinomas." Mod Pathol 10(2): 142-8.

Zwick, E., J. Bange and A. Ullrich (2001). "Receptor tyrosine kinase signalling as a target for cancer intervention strategies." Endocr Relat Cancer 8(3): 161-73.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
系統版面圖檔 系統版面圖檔