Bernard-Gallon Dominique J, Déchelotte Pierre J, Le Corre Ludovic, Vissac-Sabatier Cécile, Favy David A, Cravello Laetitia, De Latour Monique Peffault, Bignon Yves-Jean
Laboratoire d'Oncologie Moléculaire, Centre Jean Perrin, 58, rue Montalembert-B.P. 392-63011 Clermont-Ferrand.
Anticancer Res. 2003 Jan-Feb;23(1B):661-7.
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.
BRCA1和BRCA2乳腺癌易感基因是大多数遗传性乳腺癌的病因。仅在高达40 - 50%的遗传性乳腺癌家族中发现BRCA1基因突变。BRCA2基因突变与另一半遗传性乳腺癌家族以及男性乳腺癌有关。相反，尚未发现散发性乳腺肿瘤存在BRCA1和BRCA2基因突变。似乎BRCA1和BRCA2基因表达的改变可能有助于乳腺癌的发生。此外，雌激素可调节人乳腺癌细胞系中BRCA1和BRCA2的表达。我们研究了男性乳腺癌和男性乳房发育症中BRCA1和BRCA2的表达问题。我们通过免疫组织化学分析，使用一组针对BRCA1和BRCA2产生的抗体，研究了男性乳腺标本中BRCA1和BRCA2蛋白的存在情况。每种抗体的特异性已通过来自不同来源的细胞系中的蛋白质印迹法进行了验证。对6种抗BRCA1抗体的特性分析显示，在已知过表达BRCA1的乳腺细胞系（MDA - MB 231、HBL 100、T - 47D和MCF7）或急性白血病（MOLT 4）中检测到一种200 kDa的BRCA1蛋白。所有5种抗BRCA2抗体在HBL100和MCF7乳腺细胞系中检测到一种384 kDa的BRCA2蛋白。通过免疫组织化学，我们发现男性乳房发育症以及散发性和遗传性男性乳腺癌中，BRCA1和BRCA2蛋白表达存在细胞核、核周、内质网、高尔基体囊泡、分泌和顶端细胞质染色。我们报告了BRCA1和BRCA2蛋白在男性乳腺癌和男性乳房发育症的乳腺细胞不同区室中的广泛表达。这与BRCA1和BRCA2在人乳腺细胞中的雌激素依赖性表达一致。
