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 Z Zelent, Nicholas R. Lemoine, Simak Ali, Laki Buluwela

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Repressor Proteins
Zinc Fingers
Androgen Receptors
Androgens
Genes
Prostatic Neoplasms
Proteins
Androgen Antagonists
Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Transcription Factors
Ligands

Keywords

  • Androgen receptor
  • Gene expression
  • PLZF
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Pike, J., Holmes, D., Kamalati, T., Davies, D., Tolhurst, R., Mazhar, D., ... Buluwela, L. (2004). Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor. Oncogene, 23(45), 7561-7570. https://doi.org/10.1038/sj.onc.1208030

Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor. / Pike, Joanna; Holmes, David; Kamalati, Tahereh; Davies, Derek; Tolhurst, Robert; Mazhar, Danish; Fishpool, Sam; Al-Jehani, Rajai; Waxman, Jonathan; Zelent, Arthur Z; Lemoine, Nicholas R.; Ali, Simak; Buluwela, Laki.

In: Oncogene, Vol. 23, No. 45, 30.09.2004, p. 7561-7570.

Research output: Contribution to journalArticle

Pike, J, Holmes, D, Kamalati, T, Davies, D, Tolhurst, R, Mazhar, D, Fishpool, S, Al-Jehani, R, Waxman, J, Zelent, AZ, Lemoine, NR, Ali, S & Buluwela, L 2004, 'Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor', Oncogene, vol. 23, no. 45, pp. 7561-7570. https://doi.org/10.1038/sj.onc.1208030
Pike J, Holmes D, Kamalati T, Davies D, Tolhurst R, Mazhar D et al. Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor. Oncogene. 2004 Sep 30;23(45):7561-7570. https://doi.org/10.1038/sj.onc.1208030
Pike, Joanna ; Holmes, David ; Kamalati, Tahereh ; Davies, Derek ; Tolhurst, Robert ; Mazhar, Danish ; Fishpool, Sam ; Al-Jehani, Rajai ; Waxman, Jonathan ; Zelent, Arthur Z ; Lemoine, Nicholas R. ; Ali, Simak ; Buluwela, Laki. / Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor. In: Oncogene. 2004 ; Vol. 23, No. 45. pp. 7561-7570.
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