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
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...
September 30, 2004: Oncogene