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

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1496-1502
Number of pages7
JournalCancer Research
Volume62
Issue number5
Publication statusPublished - Mar 1 2002
Externally publishedYes

Fingerprint

Androgen Receptors
Prostatic Neoplasms
Missense Mutation
Androgens
Progesterone
human AR protein
Estradiol
Yeasts
Ligands
Mutation
Growth
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Shi, X. B., Ma, A. H., Xia, L., Kung, H. J., & De Vere White, R. W. (2002). Functional analysis of 44 mutant androgen receptors from human prostate cancer. Cancer Research, 62(5), 1496-1502.

Functional analysis of 44 mutant androgen receptors from human prostate cancer. / Shi, Xu Bao; Ma, Ai Hong; Xia, Liang; Kung, Hsing Jien; De Vere White, Ralph W.

In: Cancer Research, Vol. 62, No. 5, 01.03.2002, p. 1496-1502.

Research output: Contribution to journalArticle

Shi, XB, Ma, AH, Xia, L, Kung, HJ & De Vere White, RW 2002, 'Functional analysis of 44 mutant androgen receptors from human prostate cancer', Cancer Research, vol. 62, no. 5, pp. 1496-1502.
Shi XB, Ma AH, Xia L, Kung HJ, De Vere White RW. Functional analysis of 44 mutant androgen receptors from human prostate cancer. Cancer Research. 2002 Mar 1;62(5):1496-1502.
Shi, Xu Bao ; Ma, Ai Hong ; Xia, Liang ; Kung, Hsing Jien ; De Vere White, Ralph W. / Functional analysis of 44 mutant androgen receptors from human prostate cancer. In: Cancer Research. 2002 ; Vol. 62, No. 5. pp. 1496-1502.
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