ACTR/AIB1/SRC-3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes

Abstract

Co-factor ACTR is frequently overexpressed and/or amplified in multiple types of tumors. The mechanism of its function in prostate cancer (CaP) is still unclear. The effects of ACTR and androgen receptor (AR) depletion on cell proliferation and gene expression and their functions were analyzed in a panel of androgen-dependent and -independent CaP cells and CWR22 xenograft. ACTR and AR, but not TIF2, are required for proliferation of androgen-dependent and -independent cells, and for tumor growth. While AR depletion inhibited the expression of cyclin D1, cyclin B, and cdc2, ACTR depletion reduced the expression of cyclin E and cdk2. In response to serum stimulation, AR and ACTR are recruited to the corresponding target gene promoters to activate their expression in androgen-independent manner. These findings suggest that AR and ACTR may play important roles in androgen ablation resistance by controlling key cell cycle gene expression.