Androgen receptor (AR) NH2- and COOH-terminal interactions result in the differential influences on the AR-mediated transactivation and cell growth

Cheng Lung Hsu, Yuh Ling Chen, Huei Ju Ting, Wen Jye Lin, Zhiming Yang, Yanqing Zhang, Liang Wang, Chun Te Wu, Hong Chiang Chang, Shuyuan Yeh, Sanjay W. Pimplikar, Chawnshang Chang

研究成果: Article同行評審

54 引文 斯高帕斯(Scopus)

摘要

Early reports showed that androgen receptor (AR) NH2- and COOH-terminal (N-C) interaction was important for full AR function. However, the influence of these interactions on the AR in vivo effects remains unclear. Here we tested some AR-associated peptides and coregulators to determine their influences on AR N-C interaction, AR transactivation, and AR coregulator function. The results showed that AR coactivators such as ARA70N, gelsolin, ARA54, and SRC-1 can enhance AR transactivation but showed differential influences on the N-C interaction. In contrast, AR corepressors ARA67 and Rad9 can suppress AR transactivation, with ARA67 enhancing and Rad9 suppressing AR N-C interaction. Furthermore, liganded AR C terminus-associated peptides can block AR N-C interaction, but only selective peptides can block AR transactivation and coregulator function. We found all the tested peptides can suppress prostate cancer LNCaP cell growth at different levels in the presence of 5α-dihydrotestosterone, but only the tested FXXLF-containing peptides, not FXXMF-containing peptides, can suppress prostate cancer CWR22R cell growth. Together, these results suggest that the effects of AR N-C interactions may not always correlate with similar effects on AR-mediated transactivation and/or AR-mediated cell growth. Therefore, drugs designed by targeting AR N-C interaction as a therapeutic intervention for prostate cancer treatment may face unpredictable in vivo effects.

原文English
頁(從 - 到)350-361
頁數12
期刊Molecular Endocrinology
19
發行號2
DOIs
出版狀態Published - 2005 二月

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

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