SRC-3 Is Required for Prostate Cancer Cell Proliferation and Survival

Hai-Jun Zhou, Jun Yan, Weiping Luo, Gustavo Ayala, Sue-Hwa Lin, Halime Erdem, Michael Ittmann, Sophia Y. Tsai, Ming-Jer Tsai
2005 Cancer Research  
Prostate cancer is the most common cancer in men in America. Currently, steroid receptor coactivators have been proposed to mediate the development and progression of prostate cancer, at times in a steroid-independent manner. Steroid receptor coactivator-3 (SRC-3, p/CIP, AIB1, ACTR, RAC3, and TRAM-1) is a member of the p160 family of coactivators for nuclear hormone receptors including the androgen receptor. SRC-3 is frequently amplified or overexpressed in a number of cancers. However, the
more » ... of SRC-3 in cancer cell proliferation and survival is still poorly understood. In this study, we show that SRC-3 is overexpressed in prostate cancer patients and its overexpression correlates with prostate cancer proliferation and is inversely correlated with apoptosis. Consistent with patient data, we have observed that reduction of SRC-3 expression by small interfering RNA decreases proliferation, delays the G 1 -S transition, and increases cell apoptosis of different prostate cancer cell lines. Furthermore, with decreased SRC-3 expression, proliferating cell nuclear antigen and Bcl-2 expression, as well as bromodeoxyuridine incorporation in prostate cancer cells are reduced. Finally, knockdown of SRC-3 with inducible short hairpin RNA expression in prostate cancer cells decreased tumor growth in nude mice. Taken together, these findings indicate that SRC-3 is an important regulator of prostate cancer proliferation and survival. (Cancer Res 2005; 65(17): 7976-83) Requests for reprints: Ming-Jer Tsai,
doi:10.1158/0008-5472.can-04-4076 pmid:16140970 fatcat:633z6i7fpfdcdj4t34w37r7xj4