Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone
Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone
复制标题
DOI：
10.1677/joe.0.1790055
复制
发表时间：
2003-10-01
影响因子：
4
通讯作者：
El-Mowafy, AM
中科院分区：
文献类型：
--
作者：
Alkhalaf, M;El-Mowafy, AM
我们最近的研究表明，孕酮对乳腺癌细胞的生长抑制是由于诱导细胞分化，而不是凋亡。由于肿瘤抑制蛋白p53在正常细胞生长和肿瘤抑制中起着核心作用，我们研究了黄体酮对MCF-7细胞中该蛋白水平的影响。我们在这里表明，黄体酮的抗增殖作用伴随着内源性p53蛋白的下调。为了研究在p53蛋白水平正常的情况下黄体酮对细胞生长的影响，我们采用瞬时转染法过表达p53蛋白。在巨细胞病毒启动子的控制下，用含有p53人cDNA的p53表达载体转染MCF-7细胞。转染细胞暴露于100 nM黄体酮6天后，分析细胞生长、细胞活力和凋亡情况。我们在这里发现，黄体酮显著增强过表达p53的MCF-7细胞的生长抑制和凋亡，但在转染对照载体的细胞中没有。这些数据表明，在MCF-7乳腺癌细胞中重建p53功能使它们对黄体酮的生长抑制作用更敏感。
We have recently shown that growth inhibition of breast cancer cells by progesterone is due to the induction of cell differentiation, but not apoptosis. Because the tumor suppressor protein p53 plays a central role in normal cell growth and in tumor suppression, we have examined the effect of progesterone on the levels of this protein in MCF-7 cells. We show here that the antiproliferative effect of progesterone is accompanied with down-regulation of endogenous p53 protein. To study the effect of progesterone on cell growth in the presence of normal levels of p53 protein, we used transient transfection to overexpress p53 protein. MCF-7 cells were transfected with a p53 expressing vector that contains p53 human cDNA under the control of a cytomegalovirus promoter. Cell growth, cell viability, and apoptosis were analyzed in the transfected cells after six days of exposure to 100 nM progesterone. We show here that progesterone significantly enhances growth inhibition and apoptosis in MCF-7 cells overexpressing p53, but not in cells transfected with the control vector. These data suggest that re-establishing p53 function in MCF-7 breast cancer cells renders them more sensitive to the growth inhibitory effect of progesterone.