Estrogen receptor α mediates proliferation of breast cancer MCF-7 cells via a p21/PCNA/E2F1-dependent pathway
Estrogen receptor α mediates proliferation of breast cancer MCF-7 cells via a p21/PCNA/E2F1-dependent pathway
复制标题
DOI：
10.1111/febs.12658
复制
发表时间：
2014-02-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Tong-Cun
中科院分区：
文献类型：
--
作者：
Liao, Xing-Hua;Lu, Da-Lin;Zhang, Tong-Cun
雌激素受体α（ER α）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，ER α控制乳腺癌细胞增殖的确切分子机制尚不清楚。在这里，我们报告说，ER α调节细胞周期，通过抑制p53/p21和上调增殖细胞核抗原（PCNA）和增殖相关的Ki-67抗原（Ki-67），以促进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ER α诱导的MCF-7细胞增殖。ER α基因敲除可显著影响PCNA/Ki-67和p53/p21的表达。此外，ER α以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，即ER α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ER α对乳腺癌增殖的潜在影响提供了新的见解。
High expression of estrogen receptor alpha (ER alpha) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ER alpha controls breast cancer cell proliferation is not clear. Here we report that ER alpha 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-beta-estradiol (E2) enhances ER alpha-induced proliferation of MCF-7 cells by stimulating expression of PCNA and Ki-67. Knockdown of ER alpha significantly affects PCNA/Ki-67 and p53/p21 expression. Furthermore, ER alpha inhibits the transcriptional activity of p53/p21 in an estrogen response element-dependent manner. More importantly, we provide new evidence that ER alpha 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 ER alpha on breast cancer proliferation.