Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells.
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.
Horiuchi
Shinji
S
Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu,Oita,874-0838, Japan.
Kato
Kiyoko
K
Suga
Shin
S
Takahashi
Akira
A
Ueoka
Yousuke
Y
Arima
Takahiro
T
Nishida
Jun-ichi
J
Hachisuga
Toru
T
Kawarabayashi
Tatsuhiko
T
Wake
Norio
N
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D041681:NIH 3T3 Cells; D009570:Nitriles / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D002070:Butadienes; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D002867:Chromones; D047628:Estrogen Receptor alpha; D009025:Morpholines; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; C113580:U 0126; C097314:progesterone receptor B; D050760:Cyclin-Dependent Kinase Inhibitor p27; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000242:Cyclic AMP