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Quantification of BRCA1 protein in sporadic breast carcinoma with or without loss of heterozygosity of the BRCA1 gene
Author(s) -
Rio Pascale G.,
Maurizis JeanClaude,
Peffault de Latour Monique,
Big YvesJean,
BernardGallon Dominique J.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990315)80:6<823::aid-ijc5>3.0.co;2-3
Subject(s) - loss of heterozygosity , biology , breast cancer , gene product , cancer research , gene , tumor suppressor gene , gene expression , allele , breast carcinoma , carcinoma , cancer , microbiology and biotechnology , carcinogenesis , genetics
In sporadic breast cancer, no mutations of the BRCA1 gene have been reported so far, whereas BRCA1 mRNA is markedly decreased in invasive breast cancer. To elucidate the contribution of the BRCA1 gene in sporadic breast cancer, we quantified the BRCA1 protein, using [ 125 I] labeling of whole‐cell proteins, lentil‐lectin affinity chromatography, immunoprecitation by anti‐BRCA1 antibodies (C‐20, D‐20, I‐20 and K‐18), purification of the immune complex by protein A affinity chromatography and chromato‐focusing. As loss of 1 allele may lead to a decreased expression of the gene, 10 tumors were previously checked for loss of heterozygosity (LOH) of the BRCA1 gene, using 3 intragenic microsatellite markers. Our results indicated that the BRCA1 gene product was decreased in the 4 tumors with LOH compared with matched normal breast tissues. Reduced amounts of BRCA1 protein were also detected in 3 of 6 tumors without LOH. Our quantitative method allowed us to demonstrate that the BRCA1 protein level was decreased in sporadic invasive breast carcinomas with or without LOH of the BRCA1 gene, implying multiple mechanisms of BRCA1 expression down‐regulation in these tumors. Our data suggest that the amount of BRCA1 protein present may play an important role in human sporadic breast carcinoma. Int. J. Cancer 80:823–826, 1999. © 1999 Wiley‐Liss, Inc.