Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Campbell, E.J., McDuff, E., Tatarov, O., Tovey, S., Brunton, V.G., Cooke, T.G. and Edwards, J. (2008) Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer. British Journal of Cancer, 99(11), pp. 1769-1774. (doi:10.1038/sj.bjc.6604768)

Campbell, E.J., McDuff, E., Tatarov, O., Tovey, S., Brunton, V.G., Cooke, T.G. and Edwards, J. (2008) Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer. British Journal of Cancer, 99(11), pp. 1769-1774. (doi:10.1038/sj.bjc.6604768)

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Publisher's URL: http://dx.doi.org/10.1038/sj.bjc.6604768

Abstract

Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome.

Item Type:Articles
Keywords:ER-positive breast cancer, c-Src activation, nuclear, tamoxifen
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cooke, Prof Timothy and Edwards, Professor Joanne and Tovey, Ms Sian
Authors: Campbell, E.J., McDuff, E., Tatarov, O., Tovey, S., Brunton, V.G., Cooke, T.G., 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:0007-0920
ISSN (Online):1532-1827
Published Online:18 November 2008
Copyright Holders:Copyright © 2008 Nature Publishing Group
First Published:First published in British Journal of Cancer 99(11):1769-1774
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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