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Updated: Jul 19, 2026

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
A role for BRCA1 in sporadic breast cancer
J A Fraser1, J R Reeves, P D Stanton
1University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK.
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 (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 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 110 kDa 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.
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