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

doi:10.1038/sj.onc.1208030

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 journal › Article › peer-review

10 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 language	English (US)
Pages (from-to)	7561-7570
Number of pages	10
Journal	Oncogene
Volume	23
Issue number	45
DOIs	https://doi.org/10.1038/sj.onc.1208030
State	Published - Sep 30 2004
Externally published	Yes

Keywords

Androgen receptor
Gene expression
PLZF
Prostate cancer

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1208030

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title = "Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor",

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.",

keywords = "Androgen receptor, Gene expression, PLZF, Prostate cancer",

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

note = "Funding Information: We are grateful to members of the group for continual advice and support. This work was carried out with support from the Charing Cross & Hammersmith Hospitals Trustees, the Prostate Cancer Charity, Cancer Research UK and the Association for International Cancer Research.",

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doi = "10.1038/sj.onc.1208030",

language = "English (US)",

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AU - Pike, Joanna

AU - Holmes, David

AU - Kamalati, Tahereh

AU - Davies, Derek

AU - Tolhurst, Robert

AU - Mazhar, Danish

AU - Fishpool, Sam

AU - Al-Jehani, Rajai

AU - Waxman, Jonathan

AU - Zelent, Arthur

AU - Lemoine, Nicholas R.

AU - Ali, Simak

AU - Buluwela, Laki

N1 - Funding Information: We are grateful to members of the group for continual advice and support. This work was carried out with support from the Charing Cross & Hammersmith Hospitals Trustees, the Prostate Cancer Charity, Cancer Research UK and the Association for International Cancer Research.

PY - 2004/9/30

Y1 - 2004/9/30

N2 - 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.

AB - 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.

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KW - Gene expression

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KW - Prostate cancer

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

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