Int J Biol Sci 2009; 5(3):256-264. doi:10.7150/ijbs.5.256
The Role of SRC-1 in Murine Prostate Carcinogenesis Is Nonessential due to a Possible Compensation of SRC-3/AIB1 Overexpression
1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
The androgen and androgen receptor (AR)-regulated gene expression plays important roles in normal prostate and prostate cancer development, and AR transcriptional control of genes is mediated by transcriptional coactivators, including the three members of the steroid receptor coactivator (SRC) family, SRC-1 (NCOA1), SRC-2 (TIF2/GRIP1/NCOA2) and SRC-3 (AIB1, ACTR/RAC3/NCOA3). SRC-1 and SRC-3 are overexpressed in multiple human endocrine cancers and knockdown of either one of them in prostate cancer cell lines impedes cellular proliferation. Knockout of SRC-3 in mice suppresses the progression of spontaneous prostate carcinogenesis. In this study, we investigated SRC-1 contribution to prostate cancer in vivo by deleting the SRC-1 gene in TRAMP mice, which contain the probasin promoter-driven SV40 T/t antigen transgene. In assessing tumor mass of mice at various ages, we found that initiation and progression of prostate cancer induced by SV40 T/t antigens were unaltered in SRC-1-/- mice versus WT mice. Primary tumor histology and metastasis to distant lymph nodes were also similar in these mice at all time points assessed. These results demonstrate that the role of SRC-1 in mouse prostate carcinogenesis is nonessential and different from the essential contribution of SRC-3 that is required for prostate cancer progression and metastasis in mice. Interestingly, we observed that during prostate tumorigenesis SRC-1 expression was relatively constant, while SRC-3 expression was significantly elevated. Therefore, the loss of SRC-1 function may be compensated by SRC-3 overexpression during prostate tumorigenesis in SRC-1-/- mice.
Keywords: SRC-1, SRC-3, AIB1, prostate cancer
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How to cite this article:
Tien JCY, Zhou S, Xu J. The Role of SRC-1 in Murine Prostate Carcinogenesis Is Nonessential due to a Possible Compensation of SRC-3/AIB1 Overexpression. Int J Biol Sci 2009; 5(3):256-264. doi:10.7150/ijbs.5.256. Available from http://www.ijbs.com/v05p0256.htm