17 beta-estradiol-mediated growth inhibition of MDA-MB-468 cells stably transfected with the estrogen receptor: Cell cycle effects

被引:25
作者
Wang, WL
Smith, R
Burghardt, R
Safe, SH
机构
[1] TEXAS A&M UNIV,DEPT VET PHYSIOL & PHARMACOL,COLLEGE STN,TX 77843
[2] TEXAS A&M UNIV,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
[3] TEXAS A&M UNIV,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843
[4] TEXAS A&M UNIV,DEPT VET ANAT & PUBL HLTH,COLLEGE STN,TX 77843
关键词
estradiol; growth inhibition; MDA-MB-468; cells;
D O I
10.1016/S0303-7207(97)00142-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Estrogen receptor (ER)-negative MDA-MB-468 human breast cancer cells were stably transfected with wild-type human ER and utilized as a model for investigating estrogen-and aryl hydrocarbon (Ah)-responsiveness. Treatment of the stably transfected cells with 10 nM 17 beta-estradiol (E2) resulted in a significant inhibition (> 60%) of cell proliferation and DNA synthesis, which was blocked by 10(-7) M ICI 182780. Analysis by flow cytometry indicated that treatment with E2 increased the percentage of cells in G0/G1 (from 68.8 to 89.4) and decreased cells in S (from 18.4 to 3.4) and G2/M (from 12.8 to 7.2) phases of the cell cycle. The effects of E2 on the major cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors, retinoblastoma protein (RE), E2F-1, and cyclin-dependent kinase activities were also investigated in the stably transfected MDA-MB-468 cells. The results demonstrated that the growth inhibitory effects of 10(-8) M E2 in ER stably transfected MDA-MB-468 cells were associated with modulation of several factors required for cell cycle progression and DNA synthesis, including significant induction of the cyclin-dependent kinase inhibitor p21(cip-1) (> 4-fold increase after 12 h) and decreased E2F1 and PCNA. protein levels. These results show that the growth-inhibitory effects of E2 in the stably transfected cells were due to multiple factors which result in growth arrest in G0/G1 and inhibition of DNA synthesis. (C) 1997 Elsevier Science Ireland Ltd.
引用
收藏
页码:49 / 62
页数:14
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