2000 Fiscal Year Final Research Report Summary
Role of PPARγ in the growth, differentiation and apoptosis of gastrointestinal epithelial cells.
| Project/Area Number |
11670502
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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 | Osaka University |
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Principal Investigator |
MIYAZAKI Yoshiji Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30303960)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Shinji Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
TSUTSUI Syusaku Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
SHINOMURA Yasuhisa Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
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| Project Period (FY) |
1999 – 2000
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| Keywords | PPARγ / HB-EGF / amphiregulin / cyclin D1 / AP-1 / Ets / growth / differentiation |
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| Research Abstract |
Several colonic and gastric cancer cell lines express peroxisome proliferator activated receptor γ (PPARγ), a member of the nuclear receptor superfamily. The purpose of the present study was to clarify the role of PPARγ in the growth and differentiation of gastrointestinal epithelial cells and to evaluate the possibility that ligands for PPARγ can be effective for the treatment of gastrointestinal carcinoma.
1. Activation of PPARγ inhibits the growth of HT-29 colonic cancer cells and induces the differentiation markers.
2. Ligand activation of PPARγ reduces the expression of c-Met tyrosine kinase at the transcriptional level. This may be one mechanism, by which activation of PPARγ inhibits the growth of MKN-45 gastric cancer cells.
3. We created a cell line, IECrasPR82 that expresses both oncogenic ras and PPARγ by DNA transfection. Activation of PPARγ inhibits the growth of this cell line.
4. Ligands for PPARγ inhibit the expression of heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and cyclin D1 through the suppression of AP-1 and Ets.
5. Thus PPARγ ligands may be candidates for a novel approach to the treatment of gastric and colorectal cancers.
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Research Products
(12 results)
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[Publications] N.Sawada-Hase, T.Kiyohara, J.Miyagawa, H.Ueyama, H.Nishibayashi, Y.Murayama, T.Kashihara^*, M.Nakahara, Y.Miyazaki, R.Nezu^*, Y.Shinomura, Y.Matsuzawa: "An increased number of CD40-high monocytes in patients with Crohn's disease."Am.J.Gastroenterol.. 95(6). 1516-1523 (2000)
Description
「研究成果報告書概要(欧文)」より
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