Kubista Marion, Rosner Margit, Kubista Ernst, Bernaschek Gerhard, Hengstschläger Markus
Prenatal Diagnosis and Therapy, Obstetrics and Gynecology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Oncogene. 2002 Jul 18;21(31):4747-56. doi: 10.1038/sj.onc.1205580.
Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.
小鼠Brca1在不同组织的发育过程中广泛表达。目前尚不清楚BRCA1的改变为何会特异性地导致乳腺癌和卵巢癌。在此我们表明，在HC11细胞的乳腺上皮分化过程中、C2C12成肌细胞分化为肌管的过程中以及N1E-115细胞的神经元分化过程中，Brca1蛋白表达上调。BRCA1的异位过表达和内源性Brca1表达的下调特异性地影响乳腺上皮细胞分化的调控。高异位BRCA1表达时乳腺上皮细胞分化加速并非这种肿瘤抑制因子的抗增殖能力所致，且与功能性p53无关。缺乏大的中央外显子11的BRCA1变体的过表达对乳腺上皮细胞分化没有影响。这些数据为Brca1的细胞作用提供了新的见解。
