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

Journal Article · Sun May 01 04:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.01.003· OSTI ID:20717585

Horiuchi, Shinji ^[1]; Kato, Kiyoko ^[2]; Suga, Shin ^[2]; Takahashi, Akira ^[2]; Ueoka, Yousuke ^[2]; Arima, Takahiro ^[2]; Nishida, Jun-ichi ^[2]; Hachisuga, Toru; Kawarabayashi, Tatsuhiko ^[3]; Wake, Norio ^[2]

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1. Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu, Oita, 874-0838 (Japan) and Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Jyounanku Fukuoka 814-0180 (Japan)
2. Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu, Oita, 874-0838 (Japan)
3. Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Jyounanku Fukuoka 814-0180 (Japan)

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.

• OSTI ID: 20717585
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 305; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
AMP
CALVES
CELL CYCLE
CELL PROLIFERATION
CELL TRANSFORMATIONS
ESTROGENS
GENE REGULATION
GROWTH
INHIBITION
PROGESTERONE
RECEPTORS