Androgenic up-regulation of androgen receptor cDNA expression in androgen-independent prostate cancer cells

Jia Le Dai, Carol A. Maiorino, Peter J. Gkonos, Kerry L. Burnstein

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

The expression of the androgen receptor (AR) gene is regulated by androgens. Although androgens down-regulate AR mRNA in most cell lines and tissues, including the prostate, up-regulation occurs in some tissues. Androgen-mediated reduction in AR mRNA is reproduced in COSI cells and in the androgen-sensitive human prostate cancer cell line LNCaP when each expresses the AR cDNA. We have previously established that the AR cDNA contains the requisite sequences for this down-regulation. Here we shown that androgen promoted up-regulation of AR mRNA in two androgen-dependent human prostate cancer cell lines, PC3 and DU 145, when each was transfected with a human AR cDNA. This effect was due to the AR cDNA and not to the heterologous promoter driving AR protein levels in PC3 cells stably expressing an AR cDNA (PC3/AR). Up-regulation of AR in PC3/AR cells was accompanied by failure of this cells to undergo desensitization or inactivation of AR following prolonged (96 h) androgen administration, whereas the same condition resulted in desensitization of AR transactivation in LNCaP cells and in CV1 cells that stably express the AR cDNA. Androgen treatment PC3/AR cells resulted in induction of an androgen-regulated reporter gene (MMTV-CAT) as well as the native prostate specific antigen gene, which is silent in untransfected PC3 but is androgen up-regulated in LNCaP and in the prostate. This results suggest that ectopic expression of AR in androgen-independent prostate cancer cell lines establishes both typical and atypical androgenic response in a target gene-specific manner. Androgenic up-regulation of AR cDNA expression maybe due to distinct signalling mechanisms that influence androgen action in androgen-independent prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalSteroids
Volume61
Issue number9
DOIs
StatePublished - Sep 1996

Keywords

  • androgen
  • androgen receptor
  • cDNA
  • desensitization
  • prostate cancer
  • prostate specific antigen
  • up-regulation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

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