Planas-Silva M D, Weinberg R A
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Mol Cell Biol. 1997 Jul;17(7):4059-69. doi: 10.1128/MCB.17.7.4059.
In order to elucidate the mechanisms by which estrogens and antiestrogens modulate the growth of breast cancer cells, we have characterized the changes induced by estradiol that occur during the G1 phase of the cell cycle of MCF-7 human mammary carcinoma cells. Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. However, the p21 cdk inhibitor shifts from its association with cyclin E-cdk2 to cyclin D1-cdk4, providing an explanation for the observed activation of the cyclin E-cdk2 complexes. These results support the notion that cyclin D1 has an important role in steroid-dependent cell proliferation and that estrogen, by regulating the activities of G1 cyclin-dependent kinases, can control the proliferation of breast cancer cells.
为了阐明雌激素和抗雌激素调节乳腺癌细胞生长的机制，我们已对17β-雌二醇诱导的变化进行了特征描述，这些变化发生在MCF-7人乳腺癌细胞周期的G1期。添加17β-雌二醇可解除他莫昔芬处理所造成的细胞周期阻滞，导致细胞周期蛋白E-cdk2复合物在6小时内显著激活，以及视网膜母细胞瘤蛋白磷酸化。细胞周期蛋白D1水平显著增加，而细胞周期蛋白E、cdk2以及p21和p27 cdk抑制剂的水平相对恒定。然而，p21 cdk抑制剂从与细胞周期蛋白E-cdk2的结合转移至细胞周期蛋白D1-cdk4，这为所观察到的细胞周期蛋白E-cdk2复合物激活提供了解释。这些结果支持以下观点，即细胞周期蛋白D1在类固醇依赖性细胞增殖中具有重要作用，并且雌激素通过调节G1期细胞周期蛋白依赖性激酶的活性，能够控制乳腺癌细胞的增殖。
