Functional analysis of 44 mutant androgen receptors from human prostate cancer

Xu Bao Shi, Ai Hong Ma, Liang Xia, Hsing Jien Kung, Ralph W. De Vere White

研究成果: 雜誌貢獻文章同行評審

125 引文 斯高帕斯(Scopus)

摘要

Mutations of the androgen receptor gene are believed to contribute to the androgen-independent growth of prostate cancer cells. To date, 56 missense mutations of the androgen receptor have been identified in human prostate cancer. The functional status of most of these mutants has not yet been investigated. To address their functional properties, we generated 44 androgen receptor mutants that have been identified in human prostate cancer and used a colorimetric yeast reporter assay to analyze their transactivational activities in response to seven different ligands. We found that these mutant androgen receptors exhibited diverse transactivational activity: Seven (16%) showed loss of function, three (7%) had wild-type function, 14 (32%) had partial function, and 20 (45%) had gains of function. Five of 20 gain-of-function mutants had promiscuous activity, being transactivated by nonandrogens. We also found that the combination of estradiol and progesterone at physiological concentrations weakly or moderately activated an additional seven mutant androgen receptors. Our findings provide essential information for understanding the role of mutant androgen receptors in prostate cancer.
原文英語
頁(從 - 到)1496-1502
頁數7
期刊Cancer Research
62
發行號5
出版狀態已發佈 - 三月 1 2002
對外發佈Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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