McCall, P., Adams, C.E., 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) (PMID:23945560) (PMCID:PMC3759930)
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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 |
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Additional Information: | This article belongs to the Special Issue: Molecular Research in Urology |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Orange, Miss Clare and Edwards, Professor Joanne and Underwood, Mr Mark and Bennett, Miss Lindsay and Qayyum, Dr Tahir and Willder, Dr Jennifer and McCall, Dr Pamela |
Authors: | McCall, P., Adams, C.E., Willder, J., Bennett, L., Qayyum, T., Orange, C., Underwood, M., 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 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: | 1661-6596 |
ISSN (Online): | 1422-0067 |
Published Online: | 13 August 2013 |
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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