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)
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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 > School 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 |
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