| Project/Area Number |
14570438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
OKUMURA Toshikatsu Asahikawa Medical College, Department of General Medicine, Professor, 医学部, 教授 (60281903)
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| Co-Investigator(Kenkyū-buntansha) |
TANNO Satoshi Asahikawa Medical College, Department of General Medicine, Assistant Professor, 医学部, 講師 (30333686)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | troglitazone / cancer / p27Kip1 / proteasome / skp2 / PPARgamma / PPARgamma / 胃癌 / プロテアソーム / 細胞増殖抑制 / 分 |
|---|
| Research Abstract |
We have demonstrated that peroxisome proliferator activated receptor gamma(PPARr) ligands inhibit cell growth in gastric and pancreatic cancer cells and that p27 accumulation is essential for the growth inhibition by PPAR ligands(Takahashi et al., FEBS Lett 1999,Motomura et al., Cancer Res 2000). In the present study, we tried to clarify the precise mechanisms by which PPAR ligand stimulates the protein expression of p27. Troglitazone, a ligand for PPAR, increased the protein amount of p27 and inhibited cell growth in gastric, pancreatic and hepatic cancer cells. Lactacystin, an proteasome inhibitor, by itself similarly inhibited cell growth and increased p27 protein expression. Troglitazone potently inhibited proteasome activity. These results suggest that PPAR activation by troglitazone inhibits proteasome activity, thereby accumulating p27 protein, which in turn inhibits cell growth. We furthermore demonstrated that troglitazone suppressed skp2, an ubiqutin ligaze, expression. All these results suggest that the growth inhibition by PPAR actibvation was mediated by p27^<Kip1> accumulation which is induced by both inhibition of ubiquitylation of p27^<Kip1> and reduction of degradation activity of p27^<Kip1> by proteasome.
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