Epigenetic distortion to VDR transcriptional regulation in prostate cancer cells

Prashant K Singh, Craig Doig, Vineet K Dhiman, Bryan M Turner, Dominic J Smiraglia, Moray J Campbell

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13 Citations (Scopus)
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The current study aimed to examine the gene specific mechanisms by which the actions of the vitamin D receptor (VDR) are distorted in prostate cancer. Transcriptional responses toward the VDR ligand, 1α,25(OH)(2)D(3), were examined in non-malignant prostate epithelial cells (RWPE-1) and compared to the 1α,25(OH)(2)D(3)-recalcitrant prostate cancer cells (PC-3). Time resolved transcriptional studies for two VDR target genes revealed selective attenuation and repression of VDR transcriptional responses in PC-3 cells. For example, responses in PC-3 cells revealed suppressed responsiveness of IGFBP3 and G0S2. Furthermore, Chromatin Immunoprecipitation (ChIP) assays revealed that suppressed transcriptional responses in PC-3 cells of IGFBP3 and G0S2 were associated with selective VDR-induced NCOR1 enrichment at VDR-binding regions on target-gene promoter regions. We propose that VDR inappropriately recruits co-repressors in prostate cancer cells. Subsequent direct and indirect mechanisms may induce local DNA methylation and stable transcriptional silencing. Thus a transient epigenetic process mediated by co-repressor binding, namely, the control of H3K9 acetylation, is distorted to favor a more stable epigenetic event, namely DNA methylation. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
Original languageEnglish
Pages (from-to)258–263
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Early online date23 Oct 2012
Publication statusPublished - Jul 2013


  • NCOR1
  • Prostate cancer
  • Epigenetics
  • VDR


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