Yves-Jean Bignon

To elucidate the cellular role of BRCA2 in sporadic breast tumors, we studied the cellular localization and the expression of BRCA2 in carcinomas presenting or not allelic loss of BRCA2. The breast tumors were first classified with or without allelic loss of BRCA2 and then immunohistochemical staining was performed on tumors and matched normal tissues using antibodies raised against BRCA2. We showed that BRCA2 is found either in the nucleus or in perinuclear compartments such as the endoplasmic reticulum and the Golgi vesicles. We have earlier demonstrated the presence of BRCA1 as an exocrine secretion in the lumen of ductules in the normal mammary gland, as well as BRCA1 and BRCA2 in milk‐fat globules inside mammary‐gland ductules during lactation. Here we show that BRCA2 is present within the lumina of breast ductules, indicating that BRCA2 protein may also be secreted in the mammary gland. No correlation was found in breast tumors between the expression of BRCA2 protein and allelic loss of BRCA2. Int. J. Cancer 86:453–456, 2000.

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 [¹²⁵I] 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.