title: Expression of BRCA1 and BRCA2 in male breast cancers and gynecomastias.
abstract: BRCA1 and BRCA2 breast cancer susceptibility genes are responsible for most of the hereditary breast cancers. Mutations in BRCA1 account for up to 40-50% of families with hereditary breast cancer only. Mutations in BRCA2 are linked to the other half of inherited breast cancer families and also to male breast cancer. On the contrary, no sporadic breast tumors have been shown to harbor mutations in BRCA1 and BRCA2 genes. It seems that altered expressions of BRCA1 and BRCA2 genes may contribute to breast cancer development. Moreover, BRCA1 and BRCA2 expressions are regulated in human breast cancer cell lines by estrogen. We addressed the issue of BRCA1 and BRCA2 expression in male breast cancers and gynecomastias. We investigated the presence of BRCA1 and BRCA2 proteins in male breast specimens by immunohistochemical analysis with a panel of antibodies elicited against BRCA1 and BRCA2. The specificity of each antibody has been verified by Western blotting in cell lines from different origins. The characterization of 6 anti-BRCA1 antibodies revealed a BRCA1 200-kDa protein detected in breast cell lines (MDA-MB 231, HBL 100, T-47D and MCF7) or in an acute leukemia (MOLT 4), known to overexpress BRCA1. All 5 anti-BRCA2 antibodies detected a BRCA2 384-kDa protein in the HBL100 and MCF7 breast cell lines. By immunohistochemistry, we found nuclear, perinuclear, endoplasmic reticulum, Golgi vesicle, secretion and apical cytoplasmic stainings in gynecomastias and sporadic and hereditary male breast cancers, for BRCA1 and BRCA2 protein expressions. We report an extensive expression of BRCA1 and BRCA2 proteins in different compartments of the mammary gland cells in male breast carcinomas and gynecomastias. This is consistent with the estrogen-dependent expression of BRCA1 and BRCA2 in human breast cells.
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Centre Jean Perrin, 58, rue Montalembert-B.P. 392-63011 Clermont-Ferrand.
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Bernard-Gallon
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Déchelotte
authors.forename: Ludovic
authors.initials: L
authors.lastname: Le Corre
authors.forename: Cécile
authors.initials: C
authors.lastname: Vissac-Sabatier
authors.forename: David A
authors.initials: DA
authors.lastname: Favy
authors.forename: Laetitia
authors.initials: L
authors.lastname: Cravello
authors.forename: Monique Peffault
authors.initials: MP
authors.lastname: De Latour
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D024682:BRCA2 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D018567:Breast Neoplasms, Male / Q000235:genetics / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D006177:Gynecomastia / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D000939:Epitopes