Gudas J M, Li T, Nguyen H, Jensen D, Rauscher F J, Cowan K H
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cell Growth Differ. 1996 Jun;7(6):717-23.
BRCA1 was originally isolated as a gene that conferred susceptibility to early-onset familial breast and ovarian cancers. The function and regulation of this gene is presently unknown. Northern blot analyses using probes that recognize different regions of the BRCA1 cDNA revealed the presence of at least two distinct mRNA species. In synchronized normal and immortalized human mammary epithelial cells, BRCA1 mRNA levels were high in exponentially growing populations, decreased upon growth factor withdrawal, and subsequently increased again in late G1 just prior to S-phase entry. BRCA1 mRNA levels were found to be dramatically reduced in senescent normal human mammary epithelial cells and in normal human mammary epithelial cells treated with transforming growth factor beta 1. When considered together, these data indicate that expression of BRCA1 mRNA is highly sensitive to changes in growth conditions in vitro. BRCA1 proteins with apparent molecular weights of M(r) 210,000, 185,000, 160,000, 135,000, and 85,000, respectively, were detected at varying levels in all breast epithelial cells examined. Further molecular characterization of the nature and function of the different BRCA1 mRNAs and proteins should increase our understanding of this gene in the etiology of human breast cancers.
BRCA1最初是作为一种使携带者易患早发性家族性乳腺癌和卵巢癌的基因被分离出来的。目前，该基因的功能和调控机制尚不清楚。使用识别BRCA1 cDNA不同区域的探针进行的Northern印迹分析显示，至少存在两种不同的mRNA种类。在同步化的正常和永生化人乳腺上皮细胞中，BRCA1 mRNA水平在指数生长期群体中较高，在生长因子撤除后降低，随后在进入S期之前的G1晚期再次升高。在衰老的正常人乳腺上皮细胞和用转化生长因子β1处理的正常人乳腺上皮细胞中，发现BRCA1 mRNA水平显著降低。综合考虑这些数据表明，BRCA1 mRNA的表达对体外生长条件的变化高度敏感。在所有检测的乳腺上皮细胞中，分别检测到表观分子量为210,000、185,000、160,000、135,000和85,000的BRCA1蛋白，其水平各不相同。对不同BRCA1 mRNA和蛋白的性质及功能进行进一步的分子特征分析，应能增进我们对该基因在人类乳腺癌病因学中作用的理解。
