Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells

Farhat Khanim, Lyndon Gommersall, Victoria Wood, KL Smith, L Montalvo, Laura O'Neill, Y Xu, DM Peehl, Paul Stewart, Bryan Turner, Moray Campbell

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

We hypothesized that key antiproliferative target genes for the vitamin D receptor (VDR) were repressed by an epigenetic mechanism in prostate cancer cells resulting in apparent hormonal insensitivity. To explore this possibility, we examined nuclear receptor corepressor expression in a panel of nonmalignant and malignant cell lines and primary cultures, and found frequently elevated SMRT corepressor mRNA expression often associated with reduced sensitivity to 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)2D3). For example, PC-3 and DU-145 prostate cancer cell lines had 1.8-fold and twofold increases in SMRT mRNA relative to normal PrEC cells (P
Original languageEnglish
Pages (from-to)6712-25
Number of pages14
JournalOncogene
Volume23
Issue number40
Early online date9 Aug 2004
DOIs
Publication statusPublished - 2 Sept 2004

Bibliographical note

PubMed publication date shown as September 2004.

Keywords

  • 1 alpha,25-dihydroxyvitamin D-3
  • histone deacetylation inhibitors
  • prostate cancer
  • SMRT
  • GADD45 alpha

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