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 |
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Keywords: | ER-positive breast cancer, c-Src activation, nuclear, tamoxifen |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Edwards, Professor Joanne and Tovey, Ms Sian and Cooke, Prof Timothy |
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 > School 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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