A role for BRCA1 in sporadic breast cancer

Fraser, J.A., Reeves, J.R., Stanton, P.D., Black, D.M., Going, J.J., Cooke, T.G. and Bartlett, J.M.S. (2003) A role for BRCA1 in sporadic breast cancer. British Journal of Cancer, 88(8), pp. 1263-1270. (doi: 10.1038/sj.bjc.6600863)

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Publisher's URL: http://dx.doi.org/10.1038/sj.bjc.6600863

Abstract

To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS I 10 and MS 13). MS I 10 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecifcity. MS 13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110kDa molecule consistent with BRCA1 Delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess Delta11b splice variant production, reduced production of full- length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Going, Dr James and Cooke, Prof Timothy
Authors: Fraser, J.A., Reeves, J.R., Stanton, P.D., Black, D.M., Going, J.J., Cooke, T.G., and Bartlett, J.M.S.
Subjects:R Medicine > R Medicine (General)
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
ISSN:0007-0920

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