Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells

Munkley, J., Lafferty, N. P., Kalna, G., Robson, C. N., Leung, H. Y. , Rajan, P. and Elliott, D. J. (2015) Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells. BMC Cancer, 15(9), (doi:10.1186/s12885-015-1012-8)

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Abstract

Background: Androgens drive the onset and progression of prostate cancer (PCa) via androgen receptor (AR) signalling. The principal treatment for PCa is androgen deprivation therapy, although the majority of patients eventually develop a lethal castrate-resistant form of the disease, where despite low serum testosterone levels AR signalling persists. Advanced PCa often has hyper-activated RAS/ERK1/2 signalling thought to be due to loss of function of key negative regulators of the pathway, the details of which are not fully understood.<p></p> Methods: We recently carried out a genome-wide study and identified a subset of 226 novel androgen-regulated genes (PLOS ONE 6:e29088, 2011). In this study we have meta-analysed this dataset with genes and pathways frequently mutated in PCa to identify androgen-responsive regulators of the RAS/ERK1/2 pathway.<p></p> Results: We find the PTGER4 and TSPYL2 genes are up-regulated by androgen stimulation and the ADCY1, OPKR1, TRIB1, SPRY1 and PTPRR are down-regulated by androgens. Further characterisation of PTPRR protein in LNCaP cells revealed it is an early and direct target of the androgen receptor which negatively regulates the RAS/ERK1/2 pathway and reduces cell proliferation in response to androgens.<p></p> Conclusion: Our data suggest that loss of PTPRR in clinical PCa is one factor that might contribute to activation of the RAS/ERK1/2 pathway.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leung, Professor Hing and Elliott, Professor David and Kalna, Dr Gabriela and Rajan, Dr Prabhakar
Authors: Munkley, J., Lafferty, N. P., Kalna, G., Robson, C. N., Leung, H. Y., Rajan, P., and Elliott, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:BMC Cancer
Publisher:BioMed Central Ltd.
ISSN:1471-2407
ISSN (Online):1471-2407
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in BMC Cancer 15(9)
Publisher Policy:Reproduced under a Creative Commons License
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