Androgen receptor phosphorylation at serine 308 and serine 791 predicts enhanced survival in castrate resistant prostate cancer patients

McCall, P., Adams, C., Willder, J., Bennett, L., Qayyum, T., Orange, C., Underwood, M. and Edwards, J. (2013) Androgen receptor phosphorylation at serine 308 and serine 791 predicts enhanced survival in castrate resistant prostate cancer patients. International Journal of Molecular Sciences, 14(8), pp. 16656-16671. (doi: 10.3390/ijms140816656)

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Publisher's URL: http://dx.doi.org/10.3390/ijms140816656

Abstract

We previously reported that AR phosphorylation at serine 213 was associated with poor outcome and may contribute to prostate cancer development and progression. This study investigates if specific AR phosphorylation sites have differing roles in the progression of hormone naïve prostate cancer (HNPC) to castrate resistant disease (CRPC). A panel of phosphospecific antibodies were employed to study AR phosphorylation in 84 matched HNPC and CRPC tumours. Immunohistochemistry measured Androgen receptor expression phosphorylated at serine residues 94 (pAR<sub>94</sub>), 308 (pAR<sub>308</sub>), 650(pAR<sub>650</sub>) and 791(pAR<sub>791</sub>). No correlations with clinical parameters were observed for pAR<sub>94</sub> or pAR<sub>650</sub> in HNPC or CRPC tumours. In contrast to our previous observation with serine 213, high pAR<sub>308</sub> is significantly associated with a longer time to disease specific death (p= 0.011) and high pAR<sub>791</sub> expression significantly associated with a longer time to disease recurrence (p= 0.018) in HNPC tumours and longer time to death from disease recurrence (p= 0.040) in CRPC tumours. This observation in CRPC tumours was attenuated in high apoptotic tumours (p= 0.022) and low proliferating tumours (p= 0.004). These results demonstrate that understanding the differing roles of AR phosphorylation is necessary before this can be exploited as a target for castrate resistant prostate cancer.

Item Type:Articles
Additional Information:This article belongs to the Special Issue: Molecular Research in Urology
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bennett, Miss Lindsay and Orange, Miss Clare and Underwood, Mr Mark and Edwards, Professor Joanne and McCall, Dr Pamela and Qayyum, Dr Tahir and Willder, Dr Jennifer
Authors: McCall, P., Adams, C., Willder, J., Bennett, L., Qayyum, T., Orange, C., Underwood, M., 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
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Journal Name:International Journal of Molecular Sciences
Journal Abbr.:Int. J. Mol. Sci.
Publisher:MDPI
ISSN:1422-0067
ISSN (Online):1422-0067
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in International Journal of Molecular Sciences 14(8): 16656-16671
Publisher Policy:Reproduced under a Creative Commons License

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