Inhibition of androgen action by dehydroepiandrosterone sulfotransferase transfected in PC-3 prostate cancer cells

Jeannie Chan, Chung S. Song, Robert J. Matusik, Bandana Chatterjee, Arun K. Roy

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Age-dependent loss of androgen sensitivity of the rat liver is associated with a marked increase in dehydroepiandrosterone/hydroxysteroid sulfotransferase (rStd) activity. Sulfonated steroid hormones are known to be ineffective in binding receptor proteins. These observations suggest that intracellular androgen sulfonation can physiologically influence androgen action. We have examined the inhibitory effect of rStd on androgen action in the human prostate cancer-derived PC-3 cells transfected with the rat androgen receptor (AR) expression plasmid and two androgen-responsive promoter-reporter constructs (murine mammary tumor long-terminal repeat ligated to chloramphenicol acetyltransferase (CAT) gene and rat probasin androgen response dement (ARE) ligated to firefly luciferase (LUC) gene). Thes transfected cells were dependent on 5α-dihydrotestosterone (DHT) for the activation of both reporter genes and showed about a 200- and a 800-fold increase of CAT and LUC activity, respectively, at 10-10 M DHT over the no-hormone control. Expression of the sulfonating enzyme in this cell transfection system via the rStd expression plasmid caused a dose-dependent decline in the reporter activity with ≃ 90% inhibition of androgen action at a rStd:AR plasmid ratio of 100. From these results we conclude that irrespective of a high level of AR, changes in the Std expression can markedly alter the androgen sensitivity of target cells.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalChemico-Biological Interactions
Volume109
Issue number1-3
DOIs
StatePublished - Feb 20 1998

Keywords

  • Androgen action
  • Androgen receptor
  • Androgen response element
  • Dehydroepiandrosterone sulfotransferase
  • Gene regulation
  • Hydroxysteroid sulfotransferase

ASJC Scopus subject areas

  • Toxicology

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