Phosphorylation of androgen receptors at serine 515 is a potential prognostic marker for triple negative breast cancer

Roseweir, A. K. , McCall, P., Scott, A., Liew, B., Lim, Z., Mallon, E. A. and Edwards, J. (2017) Phosphorylation of androgen receptors at serine 515 is a potential prognostic marker for triple negative breast cancer. Oncotarget, 8(23), pp. 37172-37185. (doi: 10.18632/oncotarget.16420) (PMID:28415597) (PMCID:PMC5514900)

Abstract

1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry. pERK1/2 combined with AR-515 associated with improved cancer-specific survival (CSS, p = 0.038), decreased size (p = 0.001), invasive grade (p < 0.001), necrosis (p = 0.003), b-lymphocytes (p = 0.020), molecular subtype (p < 0.001) and estrogen receptor (ER)/progesterone receptor (PR)-status (p < 0.001). The cohort was therefore stratified into ER+ve and ER-ve patients. In ER+ve tumours, pERK1/2 combined with AR-515 associated with improved CSS (p = 0.038), smaller size (p = 0.004), invasive grade (p = 0.001), decreased b-lymphocytes (p = 0.013) and increased plasma cells (p = 0.048). In contrast, in TNBC patients, phosphorylation of AR-515 associated with poorer CSS (p = 0.007). pERK1/2 combined with AR-515 associated with decreased inflammation (p = 0.003), increased tumour stroma (p = 0.003) and tumour budding (p = 0.011), with trends towards decrease CSS (p = 0.065) and macrophage levels (p = 0.093). In Conclusions, AR-515 may be an important regulator of inflammation in breast cancer potential via ERK1/2 phosphorylation. AR-515 is a potential prognostic marker and therapeutic target for TNBC.

• Item Type: Articles
• Additional Information: This work was supported by the University of Glasgow and the Glasgow Breast Cancer Endowment Fund.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mallon, Dr Elizabeth and Roseweir, Dr Antonia and Edwards, Professor Joanne and McCall, Dr Pamela
• Authors: Roseweir, A. K., McCall, P., Scott, A., Liew, B., Lim, Z., Mallon, E. 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
• Published Online: 21 March 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Oncotarget 8(23):37172–37185
• Publisher Policy: Reproduced under a Creative Commons License