SRC-3 is required for prostate cancer cell proliferation and survival

Cancer Res. 2005 Sep 1;65(17):7976-83. doi: 10.1158/0008-5472.CAN-04-4076.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / biosynthesis
  • Acetyltransferases / genetics
  • Acetyltransferases / physiology*
  • Animals
  • Cell Growth Processes
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Down-Regulation
  • Histone Acetyltransferases
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Nuclear Receptor Coactivator 3
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / genetics
  • Oncogene Proteins / physiology*
  • Prostate-Specific Antigen
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • RNA, Small Interfering / genetics
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Trans-Activators
  • Acetyltransferases
  • Histone Acetyltransferases
  • NCOA3 protein, human
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3
  • Prostate-Specific Antigen