title: SRC-3 is required for prostate cancer cell proliferation and survival.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Weiping
authors.initials: W
authors.lastname: Luo
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ayala
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
authors.forename: Halime
authors.initials: H
authors.lastname: Erdem
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
mesh_terms: 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*
chemical_list: 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