Is PTEN loss associated with clinical outcome measures in human prostate cancer?

McCall, P., Witton, C.J., Grimsley, S., Nielsen, K.V. and Edwards, J. (2008) Is PTEN loss associated with clinical outcome measures in human prostate cancer? British Journal of Cancer, 99(8), pp. 1296-1301. (doi: 10.1038/sj.bjc.6604680)

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Inactivating PTEN mutations are commonly found in prostate cancer, resulting in an increased activation of Akt. In this study, we investigate the role of PTEN deletion and protein expression in the development of hormone-refractory prostate cancer using matched hormone-sensitive and hormone-refractory tumours. Fluorescent <i>in situ</i> hybridisation and immunohistochemistry was carried out to investigate <i>PTEN</i> gene deletion and PTEN protein expression in the transition from hormone-sensitive to hormone-refractory prostate cancer utilising 68 matched hormone sensitive and hormone-refractory tumour pairs (one before and one after hormone relapse). Heterogeneous <i>PTEN</i> gene deletion was observed in 23% of hormone sensitive tumours. This increased significantly to 52% in hormone-refractory tumours (<i>P</i>=0.044). PTEN protein expression was observed in the membrane, cytoplasm and the nucleus. In hormone sensitive tumours, low levels of cytoplasmic PTEN was independently associated with shorter time to relapse compared to high levels of PTEN (<i>P</i>=0.028, hazard ratio 0.51 (95%CI 0.27–0.93). Loss of PTEN expression in the nucleus of hormone sensitive tumours was independently associated with disease-specific survival (<i>P</i>=0.031, hazard ratio 0.52, 95%CI 0.29–0.95). The results from this study demonstrate a role for both cytoplasmic and nuclear PTEN in progression of prostate cancer to the hormone-refractory state.

Item Type:Articles
Keywords:PTEN, Akt, prostate, hormone refractory
Glasgow Author(s) Enlighten ID:Edwards, Professor Joanne and McCall, Dr Pamela
Authors: McCall, P., Witton, C.J., Grimsley, S., Nielsen, K.V., and Edwards, J.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
Publisher:Nature Publishing Group
ISSN (Online):1532-1827
Published Online:14 October 2008
Copyright Holders:Copyright © 2008 Nature Publishing Group
First Published:First published in British Journal of Cancer 99(8):1296-1301
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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