Rajan J V, Wang M, Marquis S T, Chodosh L A
Department of Molecular and Cellular Engineering, Stellar-Chance Laboratories, University of Pennsylvania School of Medicine, Philadelphia 19104-6069, USA.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13078-83. doi: 10.1073/pnas.93.23.13078.
We have analyzed the expression of the breast cancer susceptibility gene, Brca2, in mammary epithelial cells as a function of proliferation and differentiation. Our results demonstrate that Brca2 mRNA expression is tightly regulated during mammary epithelial proliferation and differentiation, and that this regulation occurs coordinately with Brca1. Specifically, Brca2 mRNA expression is up-regulated in rapidly proliferating cells; is down-regulated in response to serum deprivation; is expressed in a cell cycle-dependent manner, peaking at the G1/S boundary; and is up-regulated in differentiating mammary epithelial cells in response to glucocorticoids. In each case, an identical pattern of expression was observed for Brca1. These results indicate that proliferative stimuli modulate the mRNA expression of these two breast cancer susceptibility genes. In addition, the coordinate regulation of Brca1 and Brca2 revealed by these experiments suggests that these genes are induced by, and may function in, overlapping regulatory pathways involved in the control of cell proliferation and differentiation.
我们分析了乳腺癌易感基因Brca2在乳腺上皮细胞中的表达情况,该表达与细胞增殖和分化相关。我们的研究结果表明,Brca2 mRNA表达在乳腺上皮细胞增殖和分化过程中受到严格调控,且这种调控与Brca1协同发生。具体而言,Brca2 mRNA表达在快速增殖的细胞中上调;在血清剥夺时下调;以细胞周期依赖性方式表达,在G1/S边界达到峰值;在糖皮质激素作用下,分化的乳腺上皮细胞中表达上调。在每种情况下,Brca1均呈现相同的表达模式。这些结果表明,增殖刺激可调节这两个乳腺癌易感基因的mRNA表达。此外,这些实验所揭示的Brca1和Brca2的协同调控表明,这些基因由参与细胞增殖和分化控制的重叠调控途径诱导产生,并可能在其中发挥作用。