Abstract
Estrogens stimulate proliferation of estrogen receptor positive MCF7 breast cancer cells while ant/estrogens signal a G0/G1 growth arrest. In MCF7 cells, arrest is mediated through the CDK inhibitors p21 and p27 and through a decrease in cyclin E/CDK2 kinase activity. We found that in MCF7 cells, overexpression of cyclin E partially abrogates a tamoxifen mediated growth arrest. Overexpression of cyclin E is accompanied by a decrease in the levels of RB and CDK inhibitor p21 but an increase in CDK inhibitor p27. Cyclin E overexpression also alters the composition of E2F transcription factor complexes. The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Conversely, levels of the quiescence associated E2F/p130 complex is not detected in these cells. Expression from the E2F dependant promoter is elevated in proliferating and tamoxifen treated cyclin E over-expressing cells. This study suggests that a modest overexpression of cyclin E abrogates the tamoxifen mediated growth arrest through modification of the RB/E2F pathway. Moreover, these results provide one explanation of why some cells that express the estrogen receptor may be unresponsive to antiestrogens.
Original language | English (US) |
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Pages (from-to) | 4626-4634 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 21 |
Issue number | 30 |
DOIs | |
State | Published - Jul 11 2002 |
Keywords
- Breast cancer
- Cell cycle
- Cyclin E
- MCF7
- Tamoxifen
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics