Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor

Joanna Pike, David Holmes, Tahereh Kamalati, Derek Davies, Robert Tolhurst, Danish Mazhar, Sam Fishpool, Rajai Al-Jehani, Jonathan Waxman, Arthur Zelent, Nicholas R. Lemoine, Simak Ali, Laki Buluwela

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The androgen receptor (AR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and plays a key role in the development and progression of prostate cancer. Current therapies include the use of antiandrogens aimed at inhibiting the transcriptional activation of AR-regulated genes by AR. Here, we explore a strategy aimed at obtaining silencing of AR-regulated genes, based on the properties of the transcriptional repressor promyelocytic leukamia zinc-finger protein (PLZF). In order to do this, we have made a fusion protein between PLZF and AR, named PLZF-AR, and show that PLZF-AR is able to bring about silencing of genomically encoded AR-regulated genes and inhibit the androgen-regulated growth of LNCaP prostate cancer cells. Together, our results show that this strategy is able to bring about potent repression of AR-regulated responses and, therefore, could be of value in the development of new therapies for prostate cancer.

Original languageEnglish (US)
Pages (from-to)7561-7570
Number of pages10
JournalOncogene
Volume23
Issue number45
DOIs
StatePublished - Sep 30 2004

Keywords

  • Androgen receptor
  • Gene expression
  • PLZF
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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