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Interleukin‐4 activates androgen receptor through CBP/p300
Author(s) -
Lee Soo Ok,
Chun Jae Yeon,
Nadiminty Nagalakshmi,
Lou Wei,
Feng Siting,
Gao Allen C.
Publication year - 2008
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.20865
Subject(s) - androgen receptor , prostate cancer , gene knockdown , histone acetyltransferase , p300 cbp transcription factors , acetylation , cancer research , androgen , acetyltransferase , immunoprecipitation , chemistry , biology , microbiology and biotechnology , endocrinology , medicine , cancer , apoptosis , immunology , gene , antibody , biochemistry , histone acetyltransferases , hormone
Abstract BACKGROUND Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin‐4 (IL‐4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen‐sensitive prostate cancer cells. However, the mechanism of IL‐4 mediated AR activation has not yet been revealed. METHODS The effect of IL‐4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL‐4 on the interactions of AR and CBP/p300 was examined by co‐immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL‐4 mediated AR activation. RESULTS We found that IL‐4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL‐4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL‐4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL‐4 in prostate cancer cells. The IL‐4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION These results suggest that IL‐4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity. Prostate 69: 126–132, 2009. © 2008 Wiley–Liss, Inc.