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Divergent behavior of cyclin E and its low molecular weight isoforms to progesterone-induced growth inhibition in MCF-7 cells.

Montazeri H, Bouzari S, Azadmanesh K, Ostad SN, Ghahremani MH - Adv Biomed Res (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.

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.

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.

No MeSH data available.


Related in: MedlinePlus

EL expressing cells respond distinctly to progesterone treatment. Cells were treated with 0.1 and 1 μM of progesterone and cell proliferation was determined by XTT assay at 48h after treatment (Mean ± SD, n= 3; Two-way ANOVA, Bonferroni post-test, *P < 0.01 compared with MCF-7 3.1)
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Figure 1: EL expressing cells respond distinctly to progesterone treatment. Cells were treated with 0.1 and 1 μM of progesterone and cell proliferation was determined by XTT assay at 48h after treatment (Mean ± SD, n= 3; Two-way ANOVA, Bonferroni post-test, *P < 0.01 compared with MCF-7 3.1)

Mentions: Because cyclin E-CDK2 complex are one of the targets of progesterone in growth arrest process,[28] we used stable clone overexpressing cyclin E isoforms to address the effect of cyclin E on the responsivity to progesterone. The stable clones expressing full length cyclin E (EL), Trunc1 (T1 encoding 44 and 45 kDa), middle Trunc (Tmid encoding 40 kDa), and Trunc2 (T2 encoding 33 and 34 kDa) were used. For each isoforms, to limit clonal variations, we have used two high expresser clones (HE 1 and 2) for experiments. Our results revealed that progesterone treatment (at both 0.1 and 1 μM concentrations) had no significant effecton proliferation over a 24-h period for any of the clones (data not shown). However, at a concentration of 1 μM progesterone effectively inhibited proliferation in EL expressing clones. On the other hand, progesterone had no significant growth decrease in LMW-Es expressing cells [Figure 1]. In all the treatments, MCF-7 cell stably transfected with empty pcDNA 3.1 (MCF-7 3.1) was used as control cell line.


Divergent behavior of cyclin E and its low molecular weight isoforms to progesterone-induced growth inhibition in MCF-7 cells.

Montazeri H, Bouzari S, Azadmanesh K, Ostad SN, Ghahremani MH - Adv Biomed Res (2015)

EL expressing cells respond distinctly to progesterone treatment. Cells were treated with 0.1 and 1 μM of progesterone and cell proliferation was determined by XTT assay at 48h after treatment (Mean ± SD, n= 3; Two-way ANOVA, Bonferroni post-test, *P < 0.01 compared with MCF-7 3.1)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300599&req=5

Figure 1: EL expressing cells respond distinctly to progesterone treatment. Cells were treated with 0.1 and 1 μM of progesterone and cell proliferation was determined by XTT assay at 48h after treatment (Mean ± SD, n= 3; Two-way ANOVA, Bonferroni post-test, *P < 0.01 compared with MCF-7 3.1)
Mentions: Because cyclin E-CDK2 complex are one of the targets of progesterone in growth arrest process,[28] we used stable clone overexpressing cyclin E isoforms to address the effect of cyclin E on the responsivity to progesterone. The stable clones expressing full length cyclin E (EL), Trunc1 (T1 encoding 44 and 45 kDa), middle Trunc (Tmid encoding 40 kDa), and Trunc2 (T2 encoding 33 and 34 kDa) were used. For each isoforms, to limit clonal variations, we have used two high expresser clones (HE 1 and 2) for experiments. Our results revealed that progesterone treatment (at both 0.1 and 1 μM concentrations) had no significant effecton proliferation over a 24-h period for any of the clones (data not shown). However, at a concentration of 1 μM progesterone effectively inhibited proliferation in EL expressing clones. On the other hand, progesterone had no significant growth decrease in LMW-Es expressing cells [Figure 1]. In all the treatments, MCF-7 cell stably transfected with empty pcDNA 3.1 (MCF-7 3.1) was used as control cell line.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.

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.

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.

No MeSH data available.


Related in: MedlinePlus