Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, China; Institute of Biology and Medicine, Wuhan University of Science and Technology, China.
FEBS J. 2014 Feb;281(3):927-42. doi: 10.1111/febs.12658. Epub 2014 Jan 2.
High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up-regulating proliferating cell nuclear antigen (PCNA) and proliferation-related Ki-67 antigen (Ki-67) to promote proliferation of MCF-7 cells. In addition, 17-β-estradiol (E2) enhances ERα-induced proliferation of MCF-7 cells by stimulating expression of PCNA and Ki-67. Knockdown of ERα significantly affects PCNA/Ki-67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element-dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF-7 cells by up-regulating miR-17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation.
雌激素受体 α（ERα）的高表达与乳腺癌中与细胞增殖密切相关的不良预后相关。然而，ERα 控制乳腺癌细胞增殖的确切分子机制尚不清楚。在这里，我们报告 ERα 通过抑制 p53/p21 并上调增殖细胞核抗原（PCNA）和与增殖相关的 Ki-67 抗原（Ki-67）来调节细胞周期，从而促进 MCF-7 细胞的增殖。此外，17-β-雌二醇（E2）通过刺激 PCNA 和 Ki-67 的表达增强 ERα 诱导的 MCF-7 细胞增殖。敲低 ERα 显著影响 PCNA/Ki-67 和 p53/p21 的表达。此外，ERα 通过雌激素反应元件依赖性方式抑制 p53/p21 的转录活性。更重要的是，我们提供了新的证据表明，ERα 通过上调 miR-17 沉默 p21 的表达来介导 MCF-7 细胞的增殖。因此，这些数据为 ERα 对乳腺癌增殖的潜在影响提供了新的见解。
