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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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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DOI: https://doi.org/10.1038/sj.onc.1208030
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