Abstract
Estrogen receptor (ER)-negative MDA-MB-468 human breast cancer cells were stably transected 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 17β-estradiol (E2) resulted in a significant inhibition ( > 64%) of cell proliferation and DNA synthesis, which was blocked by 10-7 M ICI 182 780. 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 (RB), 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 E2Fl 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.
Original language | English (US) |
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Pages (from-to) | 49-62 |
Number of pages | 14 |
Journal | Molecular and cellular endocrinology |
Volume | 133 |
Issue number | 1 |
DOIs | |
State | Published - Sep 30 1997 |
Keywords
- Estradiol
- Growth inhibition
- MDA-MB-468 cells
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology