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ACTR/AIB1/SRC‐3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes
Author(s) -
Zou June X.,
Zhong Zhenyu,
Shi XuBao,
Tepper Clifford G.,
deVere White Ralph W.,
Kung HsingJien,
Chen Hongwu
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20477
Subject(s) - androgen receptor , prostate cancer , cyclin d1 , cancer research , cell growth , cyclin dependent kinase 1 , androgen , biology , prostate , cell cycle , cyclin , cyclin d2 , endocrinology , medicine , cancer , genetics , hormone
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION These findings suggest that AR and ACTR may play important roles in androgen ablation resistance by controlling key cell cycle gene expression. Prostate 66: 1474–1486, 2006. © 2006 Wiley‐Liss, Inc.