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Modulation of androgen receptor‐dependent transcription by resveratrol and genistein in prostate cancer cells
Author(s) -
Gao Shen,
Liu GuoZhen,
Wang Zhengxin
Publication year - 2003
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.10375
Subject(s) - transactivation , resveratrol , genistein , androgen receptor , prostate cancer , cancer research , endocrinology , biology , transcription factor , chemistry , medicine , pharmacology , cancer , biochemistry , gene
BACKGROUND The androgen receptor (AR) is a ligand‐activated transcription factor that mediates the biological responses of androgens in the prostate gland. This study focuses on the chemopreventive agents, resveratrol and genistein, on AR‐mediated transcription in prostate cancer cells. RESULTS We found that resveratrol and genistein activated AR‐driven gene expression at low concentrations, whereas they repressed the AR‐dependent reporter gene activity at high concentrations. We determined that resveratrol and genistein induced AR‐driven gene expression by activating the Raf–MEK–ERK kinase pathway. The ERK1 kinase phosphorylated the AR on multiple sites in vitro, but this phosphorylation event did not contribute to the resveratrol‐induced AR transactivation. CONCLUSIONS In vitro and in vivo studies have indicated that resveratrol and genistein are promising chemopreventive agents. Given the clear evidence that AR pathways are involved in the development and progression of prostate cancer, these data showed that the ability to modulate AR function would contribute the observed chemopreventive activity of resveratrol and genistein. © 2004 Wiley‐Liss, Inc.