title: Divergent behavior of cyclin E and its low molecular weight isoforms to progesterone-induced growth inhibition in MCF-7 cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Montazeri
authors.affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Bouzari
authors.affiliation: Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
keywords: Cyclin E; low molecular weight isoforms of cyclin E; progesterone; progesterone receptor