REST mediates androgen receptor actions on gene repression and predicts early recurrence in prostate cancer

Cancer Science & Therapy

ISSN: 1948-5956

Open Access

REST mediates androgen receptor actions on gene repression and predicts early recurrence in prostate cancer

International Conference on Prostate Cancer

June 22-24, 2015 Florida, USA

Charlotte Lavallee1, Jens Ceder2, Diego Iglesias-Gato1, Anders Bjartell2, Colin Collins3 and Amilcar Flores-Morales1

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

The Androgen Receptor (AR) is a key regulator of prostate differentiation as well as prostate tumorgenesis in all stages, including the growth of castration resistant tumors. The actions of the AR in the prostate are complex and include induction and repression of transcription. The mechanisms mediating AR repression of gene expression and their significance in prostate cancer carcinogenesis are poorly understood. Sequence analysis of androgen receptor occupied regions suggests a number of possible interactors with the AR, including the repressor element-1 silencing transcription factor (REST/NRSF). REST has a proposed role as a tumor suppressor and represses neuronal gene expression. Chromatin immunoprecipitation showed that AR binds chromatin regions containing well characterized cis-elements known to mediate REST transcriptional repression, while cell imaging studies confirmed that REST and AR closely co-localize in vivo. Androgen-induced gene repression also involves modulation of REST protein turnover through actions on the ubiquitin ligase β-TRCP. Gene expression profiling revealed that REST not only acts to repress neuronal genes but also genes involved in cell cycle progression, including Aurora Kinase A, that has previously been implicated in the growth of neuroendocrine-like castration-resistant tumors. The analysis of prostate cancer tissue microarrays revealed that tumors with reduced expression of REST have higher probability of early recurrence, independently of their Gleason score.

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