SRC-3 is required for prostate cancer cell proliferation and survival.
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 role 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 G1-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.
Zhou
Hai-Jun
HJ
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Yan
Jun
J
Luo
Weiping
W
Ayala
Gustavo
G
Lin
Sue-Hwa
SH
Erdem
Halime
H
Ittmann
Michael
M
Tsai
Sophia Y
SY
Tsai
Ming-Jer
MJ
D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D015536:Down-Regulation; D051548:Histone Acetyltransferases; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3; D017430:Prostate-Specific Antigen