2007 Fiscal Year Final Research Report Summary
Molecular mechanism of the PPARγ ligand-induced growth arrest in GI cancers
| Project/Area Number |
18590666
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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 (60281903)
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| Co-Investigator(Kenkyū-buntansha) |
TANNO Satoshi Asahikawa Medical College, Department of General Medicine, Associate Professor (30333686)
TAKAHASHI Nobuhiko Asahikawa Medical College, Department of General Medicine, Assistant Professor (20372279)
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| Project Period (FY) |
2006 – 2007
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| Keywords | PPARgamma / troglitazone / E-cadherin / claudin / cell invasion / MEK-ERK signal / Pancreas cancer |
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| Research Abstract |
We reported that thiazolidinediones, PPARgamma ligands, induce growth arrest, apoptosis and inhibit cell invasion in gastrointestinal cancer cells including human pancreatic cancer cells. A series of studies demonstrated that accumulation of p27 and inhibition of MEK-ERK signaling play a role in the inhibition of cell growth by PPARgamma lignads. Because E-cadherin and tight junction (TJ) proteins are known as molecules that are involved in cell growth and cell motility, we have examined in this study the effect of PPARgamma ligand on the expression of E-cadherin and TJ proteins in human pancreatic cancer cells, PK-1. Troglitazone dose-dependently up-regulated the expression of E-cadherin and claudin-4 mRNAs and proteins. MEK-ERK inhibition by PD98059 or U0126 increased expression of E-cadherin and claudin-4, and inhibited cell invasion. Since we have shown that troglitazone blocks MER-ERK signaling in PK-l cells, all these results suggest that troglitazone inhibits MEK-ERK signaling, followed by induction of E-cadherin and claudin-4, thereby inhibiting cell invasion in human pancreatic cancer cells.
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Research Products
(6 results)
