Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells

Shinji Horiuchi, Kiyoko Kato, Shin Suga, Akira Takahashi, Yousuke Ueoka, Takahiro Arima, Jun Ichi Nishida, Toru Hachisuga, Tatsuhiko Kawarabayashi, Norio Wake

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Abstract

Previously, we found a significant reduction of progesterone receptor B (PR-B) expression levels in the Ras-mediated NIH3T3 cell transformation, and re-expression of exogenous PR-B eliminated the tumorigenic potential. We hypothesized that this reduction is of biological significance in cell transformation. In the present study, we determined the correlation between PR-B expression and cell cycle progression. In synchronized NIH3T3 cells, we found an increase in PR-B protein and p27 CDK inhibitor levels in the G0/G1 phase and a reduction due to redistribution in the S and G2/M phases. The MEK inhibitor or cAMP stimulation arrested NIH3T3 cells in the G0/G1 phase of the cell cycle. The expression of PR-B and p27 CDK inhibitors was up-regulated by treatment with both the MEK inhibitor and cAMP. Treatment of synchronized cells with a PKA inhibitor in the presence of 1% calf serum resulted in a significant reduction in both PR-B and p27 levels. The decrease in the PR-B levels caused by anti-sense oligomers or siRNA corresponded to the reduction in p27 levels. PR-B overexpression by adenovirus infection induced p27 and suppressed cell growth. Finally, we showed that PR-B modulation involved in the regulation of NIH3T3 cell proliferation was independent of nuclear estrogen receptor (ER) activity but dependent on non-genomic ER activity.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalExperimental Cell Research
Volume305
Issue number2
DOIs
Publication statusPublished - May 1 2005

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Horiuchi, S., Kato, K., Suga, S., Takahashi, A., Ueoka, Y., Arima, T., Nishida, J. I., Hachisuga, T., Kawarabayashi, T., & Wake, N. (2005). Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells. Experimental Cell Research, 305(2), 233-243. https://doi.org/10.1016/j.yexcr.2005.01.003