Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/23700
標題: 白藜蘆醇抑制雄性激素受體蛋白Serine81磷酸化及活性並降低攝護腺癌細胞LNCaP的生長能力
Resveratrol Inhibited Serine 81 Phosphorylation and Activity of Androgen Receptor and Reduced Proliferation of LNCaP Prostate Cancer Cells
作者: 陳姿吟
Chen, Tzu-Yin
關鍵字: Resveratrol;白藜蘆醇;Androgen Receptor;p-S81-AR;Phosphrylation;雄性激素受體;雄性激素受體磷酸化蛋白;磷酸化
出版社: 生命科學系所
引用: 1. Gelmann, E. P. (2002) Molecular biology of the androgen receptor, J Clin Oncol 20, 3001-3015. 2. Rabasseda, X. (2004) Dutasteride: a potent dual inhibitor of 5-alpha-reductase for benign prostatic hyperplasia, Drugs Today (Barc) 40, 649-661. 3. Feldman, B. J., and Feldman, D. (2001) The development of androgen-independent prostate cancer, Nat Rev Cancer 1, 34-45. 4. Balk, S. P., Ko, Y. J., and Bubley, G. J. (2003) Biology of prostate-specific antigen, J Clin Oncol 21, 383-391. 5. Gioeli, D., Ficarro, S. B., Kwiek, J. J., Aaronson, D., Hancock, M., Catling, A. D., White, F. M., Christian, R. E., Settlage, R. E., Shabanowitz, J., Hunt, D. F., and Weber, M. J. (2002) Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites, J Biol Chem 277, 29304-29314. 6. Zhu, Z., Becklin, R. R., Desiderio, D. M., and Dalton, J. T. (2001) Identification of a novel phosphorylation site in human androgen receptor by mass spectrometry, Biochem Biophys Res Commun 284, 836-844. 7. Zhou, Z. X., Kemppainen, J. A., and Wilson, E. M. (1995) Identification of three proline-directed phosphorylation sites in the human androgen receptor, Mol Endocrinol 9, 605-615. 8. Adams, M., Meijer, O. C., Wang, J., Bhargava, A., and Pearce, D. (2003) Homodimerization of the glucocorticoid receptor is not essential for response element binding: activation of the phenylethanolamine N-methyltransferase gene by dimerization-defective mutants, Mol Endocrinol 17, 2583-2592. 9. Kraus, S., Gioeli, D., Vomastek, T., Gordon, V., and Weber, M. J. (2006) Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptor, Cancer Res 66, 11047-11054. 10. Guo, Z., Dai, B., Jiang, T., Xu, K., Xie, Y., Kim, O., Nesheiwat, I., Kong, X., Melamed, J., Handratta, V. D., Njar, V. C., Brodie, A. M., Yu, L. R., Veenstra, T. D., Chen, H., and Qiu, Y. (2006) Regulation of androgen receptor activity by tyrosine phosphorylation, Cancer Cell 10, 309-319. 11. Ponguta, L. A., Gregory, C. W., French, F. S., and Wilson, E. M. (2008) Site-specific androgen receptor serine phosphorylation linked to epidermal growth factor-dependent growth of castration-recurrent prostate cancer, J Biol Chem 283, 20989-21001. 12. Coon, J. J., Ueberheide, B., Syka, J. E., Dryhurst, D. D., Ausio, J., Shabanowitz, J., and Hunt, D. F. (2005) Protein identification using sequential ion/ion reactions and tandem mass spectrometry, Proc Natl Acad Sci U S A 102, 9463-9468. 13. Chen, S., Xu, Y., Yuan, X., Bubley, G. J., and Balk, S. P. (2006) Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1, Proc Natl Acad Sci U S A 103, 15969-15974. 14. Liu, S., Yuan, Y., Okumura, Y., Shinkai, N., and Yamauchi, H. (2010) Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth, Biochem Biophys Res Commun 394, 297-302. 15. Shigemura, K., Isotani, S., Wang, R., Fujisawa, M., Gotoh, A., Marshall, F. F., Zhau, H. E., and Chung, L. W. (2009) Soluble factors derived from stroma activated androgen receptor phosphorylation in human prostate LNCaP cells: roles of ERK/MAP kinase, Prostate 69, 949-955. 16. Baur, J. A., and Sinclair, D. A. (2006) Therapeutic potential of resveratrol: the in vivo evidence, Nat Rev Drug Discov 5, 493-506. 17. Aggarwal, B. B., Bhardwaj, A., Aggarwal, R. S., Seeram, N. P., Shishodia, S., and Takada, Y. (2004) Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies, Anticancer Res 24, 2783-2840. 18. Wang, Y., Romigh, T., He, X., Orloff, M. S., Silverman, R. H., Heston, W. D., and Eng, C. (2010) Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines, Hum Mol Genet 19, 4319-4329. 19. Aziz, M. H., Nihal, M., Fu, V. X., Jarrard, D. F., and Ahmad, N. (2006) Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3''-kinase/Akt pathway and Bcl-2 family proteins, Mol Cancer Ther 5, 1335-1341. 20. Pervaiz, S. (2003) Resveratrol: from grapevines to mammalian biology, FASEB J 17, 1975-1985. 21. Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W., Fong, H. H., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., Moon, R. C., and Pezzuto, J. M. (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes, Science 275, 218-220. 22. Jang, M., and Pezzuto, J. M. (1999) Cancer chemopreventive activity of resveratrol, Drugs Exp Clin Res 25, 65-77. 23. Haworth, R. S., and Avkiran, M. (2001) Inhibition of protein kinase D by resveratrol, Biochem Pharmacol 62, 1647-1651. 24. Tou, J., and Urbizo, C. (2001) Resveratrol inhibits the formation of phosphatidic acid and diglyceride in chemotactic peptide- or phorbol ester-stimulated human neutrophils, Cell Signal 13, 191-197. 25. Mgbonyebi, O. P., Russo, J., and Russo, I. H. (1998) Antiproliferative effect of synthetic resveratrol on human breast epithelial cells, Int J Oncol 12, 865-869. 26. Pozo-Guisado, E., Alvarez-Barrientos, A., Mulero-Navarro, S., Santiago-Josefat, B., and Fernandez-Salguero, P. M. (2002) The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle, Biochem Pharmacol 64, 1375-1386. 27. Ragione, F. D., Cucciolla, V., Borriello, A., Pietra, V. D., Racioppi, L., Soldati, G., Manna, C., Galletti, P., and Zappia, V. (1998) Resveratrol arrests the cell division cycle at S/G2 phase transition, Biochem Biophys Res Commun 250, 53-58. 28. Mizutani, K., Ikeda, K., Kawai, Y., and Yamori, Y. (1998) Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells, Biochem Biophys Res Commun 253, 859-863. 29. Manna, S. K., Mukhopadhyay, A., and Aggarwal, B. B. (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation, J Immunol 164, 6509-6519. 30. Hsieh, T. C., and Wu, J. M. (1999) Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines, Exp Cell Res 249, 109-115. 31. Clement, M. V., Hirpara, J. L., Chawdhury, S. H., and Pervaiz, S. (1998) Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells, Blood 92, 996-1002. 32. Huang, C., Ma, W. Y., Goranson, A., and Dong, Z. (1999) Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway, Carcinogenesis 20, 237-242. 33. Chen, Q., Ganapathy, S., Singh, K. P., Shankar, S., and Srivastava, R. K. (2010) Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells, PLoS One 5, e15288. 34. Rotondo, S., Rajtar, G., Manarini, S., Celardo, A., Rotillo, D., de Gaetano, G., Evangelista, V., and Cerletti, C. (1998) Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function, Br J Pharmacol 123, 1691-1699. 35. Wadsworth, T. L., and Koop, D. R. (1999) Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages, Biochem Pharmacol 57, 941-949. 36. Lu, R., and Serrero, G. (1999) Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells, J Cell Physiol 179, 297-304. 37. Mitchell, S. H., Zhu, W., and Young, C. Y. (1999) Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells, Cancer Res 59, 5892-5895. 38. Schneider, Y., Vincent, F., Duranton, B., Badolo, L., Gosse, F., Bergmann, C., Seiler, N., and Raul, F. (2000) Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells, Cancer Lett 158, 85-91. 39. Larrosa, M., Tomas-Barberan, F. A., and Espin, J. C. (2003) Grape polyphenol resveratrol and the related molecule 4-hydroxystilbene induce growth inhibition, apoptosis, S-phase arrest, and upregulation of cyclins A, E, and B1 in human SK-Mel-28 melanoma cells, J Agric Food Chem 51, 4576-4584. 40. Kim, Y. A., Choi, B. T., Lee, Y. T., Park, D. I., Rhee, S. H., Park, K. Y., and Choi, Y. H. (2004) Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells, Oncol Rep 11, 441-446. 41. Kaneuchi, M., Sasaki, M., Tanaka, Y., Yamamoto, R., Sakuragi, N., and Dahiya, R. (2003) Resveratrol suppresses growth of Ishikawa cells through down-regulation of EGF, Int J Oncol 23, 1167-1172. 42. Poussier, B., Cordova, A. C., Becquemin, J. P., and Sumpio, B. E. (2005) Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis, J Vasc Surg 42, 1190-1197. 43. Bertelli, A. A., Giovannini, L., Stradi, R., Urien, S., Tillement, J. P., and Bertelli, A. (1998) Evaluation of kinetic parameters of natural phytoalexin in resveratrol orally administered in wine to rats, Drugs Exp Clin Res 24, 51-55. 44. Gao, S., Liu, G. Z., and Wang, Z. (2004) Modulation of androgen receptor-dependent transcription by resveratrol and genistein in prostate cancer cells, Prostate 59, 214-225. 45. Fremont, L., Belguendouz, L., and Delpal, S. (1999) Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids, Life Sci 64, 2511-2521. 46. Jang, D. S., Kang, B. S., Ryu, S. Y., Chang, I. M., Min, K. R., and Kim, Y. (1999) Inhibitory effects of resveratrol analogs on unopsonized zymosan-induced oxygen radical production, Biochem Pharmacol 57, 705-712. 47. Yuan, H., Pan, Y., and Young, C. Y. (2004) Overexpression of c-Jun induced by quercetin and resverol inhibits the expression and function of the androgen receptor in human prostate cancer cells, Cancer Lett 213, 155-163. 48. Horvath, Z., Marihart-Fazekas, S., Saiko, P., Grusch, M., Ozsuy, M., Harik, M., Handler, N., Erker, T., Jaeger, W., Fritzer-Szekeres, M., Djavan, B., and Szekeres, T. (2007) Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines, Anticancer Res 27, 3459-3464. 49. Hsu, F. N., Yang, M. S., Lin, E., Tseng, C. F., and Lin, H. (2011) The significance of Her2 on androgen receptor protein stability in the transition of androgen requirement in prostate cancer cells, Am J Physiol Endocrinol Metab 300, E902-908. 50. Lin, H., Chen, M. C., and Ku, C. T. (2009) Cyclin-dependent kinase 5 regulates steroidogenic acute regulatory protein and androgen production in mouse Leydig cells, Endocrinology 150, 396-403. 51. Lin, H., Chen, M. C., Chiu, C. Y., Song, Y. M., and Lin, S. Y. (2007) Cdk5 regulates STAT3 activation and cell proliferation in medullary thyroid carcinoma cells, J Biol Chem 282, 2776-2784. 52. Kuwajerwala, N., Cifuentes, E., Gautam, S., Menon, M., Barrack, E. R., and Reddy, G. P. (2002) Resveratrol induces prostate cancer cell entry into s phase and inhibits DNA synthesis, Cancer Res 62, 2488-2492. 53. Benitez, D. A., Pozo-Guisado, E., Alvarez-Barrientos, A., Fernandez-Salguero, P. M., and Castellon, E. A. (2007) Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines, J Androl 28, 282-293. 54. Collins, K., Jacks, T., and Pavletich, N. P. (1997) The cell cycle and cancer, Proc Natl Acad Sci U S A 94, 2776-2778. 55. Narayanan, B. A., Narayanan, N. K., Re, G. G., and Nixon, D. W. (2003) Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets, Int J Cancer 104, 204-212. 56. Shih, A., Zhang, S., Cao, H. J., Boswell, S., Wu, Y. H., Tang, H. Y., Lennartz, M. R., Davis, F. B., Davis, P. J., and Lin, H. Y. (2004) Inhibitory effect of epidermal growth factor on resveratrol-induced apoptosis in prostate cancer cells is mediated by protein kinase C-alpha, Mol Cancer Ther 3, 1355-1364. 57. Kai, L., Samuel, S. K., and Levenson, A. S. (2010) Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex, Int J Cancer 126, 1538-1548. 58. Lin, H. Y., Shih, A., Davis, F. B., Tang, H. Y., Martino, L. J., Bennett, J. A., and Davis, P. J. (2002) Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line, J Urol 168, 748-755. 59. Cardile, V., Scifo, C., Russo, A., Falsaperla, M., Morgia, G., Motta, M., Renis, M., Imbriani, E., and Silvestre, G. (2003) Involvement of HSP70 in resveratrol-induced apoptosis of human prostate cancer, Anticancer Res 23, 4921-4926. 60. Shi, W. F., Leong, M., Cho, E., Farrell, J., Chen, H. C., Tian, J., and Zhang, D. (2009) Repressive effects of resveratrol on androgen receptor transcriptional activity, PLoS One 4, e7398. 61. Lin, H. K., Yeh, S., Kang, H. Y., and Chang, C. (2001) Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor, Proc Natl Acad Sci U S A 98, 7200-7205. 62. Wen, Y., Hu, M. C., Makino, K., Spohn, B., Bartholomeusz, G., Yan, D. H., and Hung, M. C. (2000) HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway, Cancer Res 60, 6841-6845. 63. Lin, H. K., Wang, L., Hu, Y. C., Altuwaijri, S., and Chang, C. (2002) Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase, EMBO J 21, 4037-4048. 64. Nan, B., Snabboon, T., Unni, E., Yuan, X. J., Whang, Y. E., and Marcelli, M. (2003) The PTEN tumor suppressor is a negative modulator of androgen receptor transcriptional activity, J Mol Endocrinol 31, 169-183. 65. Lin, H. K., Hu, Y. C., Yang, L., Altuwaijri, S., Chen, Y. T., Kang, H. Y., and Chang, C. (2003) Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers, J Biol Chem 278, 50902-50907. 66. Lee, D. K., and Chang, C. (2003) Endocrine mechanisms of disease: Expression and degradation of androgen receptor: mechanism and clinical implication, J Clin Endocrinol Metab 88, 4043-4054. 67. Gill, C., Walsh, S. E., Morrissey, C., Fitzpatrick, J. M., and Watson, R. W. (2007) Resveratrol sensitizes androgen independent prostate cancer cells to death-receptor mediated apoptosis through multiple mechanisms, Prostate 67, 1641-1653. 68. Wang, W., Wang, H., Rayburn, E. R., Zhao, Y., Hill, D. L., and Zhang, R. (2008) 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action, Br J Cancer 98, 792-802. 69. Wang, T. T., Hudson, T. S., Wang, T. C., Remsberg, C. M., Davies, N. M., Takahashi, Y., Kim, Y. S., Seifried, H., Vinyard, B. T., Perkins, S. N., and Hursting, S. D. (2008) Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo, Carcinogenesis 29, 2001-2010. 70. Hsieh, T. C., and Wu, J. M. (2000) Grape-derived chemopreventive agent resveratrol decreases prostate-specific antigen (PSA) expression in LNCaP cells by an androgen receptor (AR)-independent mechanism, Anticancer Res 20, 225-228. 71. Jones, S. B., DePrimo, S. E., Whitfield, M. L., and Brooks, J. D. (2005) Resveratrol-induced gene expression profiles in human prostate cancer cells, Cancer Epidemiol Biomarkers Prev 14, 596-604. 72. Kim, Y. A., Rhee, S. H., Park, K. Y., and Choi, Y. H. (2003) Antiproliferative effect of resveratrol in human prostate carcinoma cells, J Med Food 6, 273-280. 73. Harada, N., Murata, Y., Yamaji, R., Miura, T., Inui, H., and Nakano, Y. (2007) Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells, J Nutr Sci Vitaminol (Tokyo) 53, 556-560. 74. Gobinet, J., Poujol, N., and Sultan, C. (2002) Molecular action of androgens, Mol Cell Endocrinol 198, 15-24. 75. Huggins, C., and Hodges, C. V. (2002) Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941, J Urol 168, 9-12. 76. Harada, N., Atarashi, K., Murata, Y., Yamaji, R., Nakano, Y., and Inui, H. (2011) Inhibitory mechanisms of the transcriptional activity of androgen receptor by resveratrol: Implication of DNA binding and acetylation of the receptor, J Steroid Biochem Mol Biol 123, 65-70. 77. Nelson, W. G., De Marzo, A. M., and Isaacs, W. B. (2003) Prostate cancer, N Engl J Med 349, 366-381. 78. Seeni, A., Takahashi, S., Takeshita, K., Tang, M., Sugiura, S., Sato, S. Y., and Shirai, T. (2008) Suppression of prostate cancer growth by resveratrol in the transgenic rat for adenocarcinoma of prostate (TRAP) model, Asian Pac J Cancer Prev 9, 7-14. 79. Harper, C. E., Patel, B. B., Wang, J., Arabshahi, A., Eltoum, I. A., and Lamartiniere, C. A. (2007) Resveratrol suppresses prostate cancer progression in transgenic mice, Carcinogenesis 28, 1946-1953. 80. Harper, C. E., Cook, L. M., Patel, B. B., Wang, J., Eltoum, I. A., Arabshahi, A., Shirai, T., and Lamartiniere, C. A. (2009) Genistein and resveratrol, alone and in combination, suppress prostate cancer in SV-40 tag rats, Prostate 69, 1668-1682. 81. Kesler, C. T., Gioeli, D., Conaway, M. R., Weber, M. J., and Paschal, B. M. (2007) Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor, Mol Endocrinol 21, 2071-2084.
摘要: 
白藜蘆醇 (resveratrol, Res) 廣泛存在於多種植物和水果之中,其中以深色葡萄的皮含有最高濃度的resveratrol含量,其次是在紅酒成分中。眾多文獻證實resveratrol有效抑制多種癌症細胞生長,因此常被應用於研究各種癌症中的治療之一。近十多年來,已有學者利用Res處理於攝護腺癌細胞,結果發現會降低雄性激素受體 (androgen receptor, AR) 表現量及功能,並影響細胞內有關凋亡蛋白的改變:抗凋亡蛋白減少,促進細胞凋亡蛋白增加,進而影響了癌細胞的增生。AR磷酸化蛋白Serine 81 (p-S81-AR) 是當有雄性激素刺激時,反應最為強烈的位置,此位置的磷酸化可被視為與AR活性上升有關,且當有低濃度雄性激素處理時,會增加p-S81-AR的穩定性。另外,有學者發現p-S81-AR可能與AR的穩定性相關。本論文研究目的是探討resveratrol透過何種機制的影響進而抑制雄性激素依賴型的攝護腺癌細胞生長。首先利用細胞計數方式證實resveratrol會減緩攝護腺癌細胞LNCaP的生長,而跟細胞週期相關蛋白中,Cyclin A和Cyclin D1皆會受其改變,經過流式細胞儀檢測觀察到細胞週期分佈停留在G1時期有較長的時間。在Western blotting分析,發現resveratrol明顯降低了p-S81-AR的蛋白表現,有趣的是,AR蛋白量卻因此而上升且在免疫沉澱法中也看到相同的情形。於是進一步利用逆轉錄聚合

Resveratrol (Res) has been existed commonly in a wide variety of fruits and plants, among them, black-grape skin contains high concentrations of resveratrol, next major constituent of red wine. Resveratrol could inhibit proliferation of several types of cancer cells. In recent years, many researchers used resveratrol in prostate cancer cells, they reported that resveratrol not only decreased androgen receptor (AR) protein expression and function, but also downrerulated the anti-apoptotic proteins and upregulated the pro-apoptotic proteins. Serine 81 (Ser81) is the highest stoichiomertric phosphorylation on AR protein and involves in stabilization of AR. In this study, we investigated that which mechanism did resveratrol affect in androgen-dependent prostate cancer cells. Our results demonstrated that resveratrol did decrease LNCaP cells proliferation. Besides we also found that resveratrol affected cell cycle regulators, such as Cyclin A, and Cyclin D1, then cell cycle was arrested G1 phase through flow cytometry. Interestingly, we observed that resveratrol decreased AR Ser81 phosphorylation but oppositely increased AR protein levels by Western blotting and immunoprecipitation in LNCaP cells. But resveratrol did not affect the AR mRNA expression. Since AR Ser81 phosphorylation was affected by resveratrol, the effects on AR upstream kinases (such as Erk and Cdk5) were investigated. The results showed Cdk5 kinase was activated after resveratrol treatment. As regards to AR transcriptional activity, we found the increase of cytosolic AR while nuclear AR was unaffected. Otherwise AR was recovery from nuclear when AR Ser81 mimicked to constinue phosphorylation (Aspartic acid 81, D81). Reporter assay and the expression of AR regulatory gene, prostate-specific antigen (PSA) were also supported the results that Res inhibited AR transcriptional activity in LNCaP cells.The AR Ser 81 phosphorylation and AR protein stability were declined by resveratrol. In conclusion, these results suggest that resveratrol might inhibit AR transcriptional activity through decreasing Ser81 phosphorylation and therefore resulted in growth inhibition of androgen-dependent prostate cancer cells.
URI: http://hdl.handle.net/11455/23700
其他識別: U0005-1508201113480500
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