Divergent behavior of cyclin E and its low molecular weight isoforms to progesterone-induced growth inhibition in MCF-7 cells
نویسندگان
1 Department of Virology, Pasteur Institute of Iran, Tehran, Iran
2 Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran
5 Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran
doi
چکیده
Background: Progesterone is a steroid hormone that modulates proliferation and differentiation in a cell phase and tissue-specific manner. Its function in breast cancer cells is of great significance since it can predict susceptibility of tumor cells to inhibitory effects of progesterone as adjuvant therapy.Materials and Methods: Stable clones overexpressing cyclin E (EL) and its low molecular weight isoforms (LMW-Es) were generated and treated with various concentrations of progesterone. Cell proliferation was assessed 24 and 48 h after the treatment. Changes in progesterone receptor (PR) expression were measured by real-time polymerase chain reaction.Results: Here we demonstrated that overexpression of EL and LMW-Es have divergent effects with regard to progesterone response. We found that progesterone could significantly decrease the growth rate of EL-expressing cells in the second cell cycle after treatment; however, progesterone was ineffective to arrest growth of LMW-Es expressing cells. PR expression level was at control level in EL-expressing cells but was downregulatedin LMW-Esexpressing clones.Conclusion: These results were in line with progesterone response of studied cells. The drop in PR expression together with altered distribution of p21 and p27 can explain different effects of cyclin E isoforms expression on progesterone responsivity. These data bring cyclin E status of cancer cells as a marker for predicting the efficacy of progesterone treatment.