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Phosphorylation of ER alpha at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ER alpha phosphorylation in breast cancer progression

Sarwar, N., Kim, J. S., Jiang, J., Peston, D., Sinnett, H. D., Madden, P., Gee, Julia Margaret Wendy, Nicholson, Robert Ian, Lykkesfeldt, A. E., Shousha, S., Coombes, R. C. and Ali, S. 2006. Phosphorylation of ER alpha at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ER alpha phosphorylation in breast cancer progression. Endocrine-Related Cancer 13 (3) , pp. 851-861. 10.1677/erc.1.01123

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Abstract

Oestrogen receptor-α (ERα) is an important prognostic marker in breast cancer and endocrine therapies are designed to inhibit or prevent ERα activity. In vitro studies have indicated that phosphorylation of ERα, in particular on serine 118 (S118), can result in activation in a ligand-independent manner, thereby potentially contributing to resistance to endocrine agents, such as tamoxifen and aromatase inhibitors. Here we report the immunohistochemistry (IHC) of S118 phosphorylation in 301 primary breast tumour biopsies. Surprisingly, this analysis shows that S118 phosphorylation is higher in more differentiated tumours, suggesting that phosphorylation at this site is associated with a good prognosis in patients not previously treated with endocrine agents. However, we also report that S118 phosphorylation was elevated in tumour biopsies taken from patients who had relapsed following tamoxifen treatment, when compared to pre-treatment biopsies. Taken together, these data are consistent with the view that S118 phosphorylation is a feature of normal ERα function and that increases in levels of phosphorylation at this site may play a key role in the emergence of endocrine resistance in breast cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Publisher: Society for Endocrinology
ISSN: 1351-0088
Last Modified: 04 Jun 2017 03:07
URI: http://orca-mwe.cf.ac.uk/id/eprint/17096

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