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p68/DdX5 Supports β-Catenin & RNAP II during Androgen Receptor Mediated Transcription in Prostate Cancer

Lookup NU author(s): Dr Emma Clark, Dr Richard Temperley, Amy Barnard, Professor Craig Robson

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Abstract

The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. beta-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear beta-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and beta-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and beta-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and beta-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and beta-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating beta-Catenin and AR transcriptional activity in PCa cells.


Publication metadata

Author(s): Clark EL, Hadjimichael C, Temperley R, Barnard A, Fuller-Pace FV, Robson CN

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2013

Volume: 8

Issue: 1

Print publication date: 17/01/2013

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0054150

DOI: 10.1371/journal.pone.0054150


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