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- Title
Silencing of androgen-regulated genes using a fusion of AR with the PLZF transcriptional repressor.
- Authors
Pike, Joanna; Holmes, David; Kamalati, Tahereh; Davies, Derek; Tolhurst, Robert; Mazhar, Danish; Fishpool, Sam; al-Jehani, Rajai; Waxman, Jonathan; Zelent, Arthur; Lemoine, Nicholas R.; Ali, Simak; Buluwela, Laki
- 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.Oncogene (2004) 23, 7561-7570. doi:10.1038/sj.onc.1208030 Published online 30 August 2004
- Subjects
PROSTATE cancer; ANDROGENS; SEX hormones; MYELOID leukemia; NONLYMPHOID leukemia; GENES; TRANSCRIPTION factors
- Publication
Oncogene, 2004, Vol 23, Issue 45, p7561
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208030