Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

Patek, S.C., Willder, J.M., Heng, J.S., Taylor, B., Horgan, P.G. , Leung, H.Y. , Underwood, M.A. and Edwards, J. (2016) Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients. Oncotarget, 8(3), pp. 4875-4887. (doi:10.18632/oncotarget.13608) (PMID:27902483)

[img]
Preview
Text
131573.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c.c. 0.469, p=0.001) and cytoplasmic pARS578 (c.c. 0.426 p=0.002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0.001 and p=0.036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0.001) and nucleus (p=0.038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0.005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Horgan, Professor Paul and Leung, Professor Hing and Heng, Dr Joanne and Underwood, Mr Mark and Edwards, Professor Joanne and Willder, Dr Jennifer and Patek, Mrs Samantha
Authors: Patek, S.C., Willder, J.M., Heng, J.S., Taylor, B., Horgan, P.G., Leung, H.Y., Underwood, M.A., and Edwards, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN:1949-2553
ISSN (Online):1949-2553
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Oncotarget 8(3):4875-7887
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record