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

Oncogene volume 23, pages 7561–7570 (2004)Cite this article

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.

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Acknowledgements

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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Author notes

  1. Joanna Pike and David Holmes: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Cancer Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK

    Joanna Pike, David Holmes, Tahereh Kamalati, Robert Tolhurst, Danish Mazhar, Sam Fishpool, Rajai al-Jehani, Jonathan Waxman, Nicholas R Lemoine, Simak Ali & Laki Buluwela

  2. Lincoln's Inn Fields Laboratories, Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Derek Davies

  3. Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK

    Arthur Zelent

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  1. Joanna Pike
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  3. Tahereh Kamalati
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Correspondence to Simak Ali or Laki Buluwela.

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Pike, J., Holmes, D., Kamalati, T. et al. Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor. Oncogene 23, 7561–7570 (2004). https://doi.org/10.1038/sj.onc.1208030

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