2006 Fiscal Year Final Research Report Summary
INVOLVEMENT OF MEMBRANE-TYPE BILE ACID RECEPTOR M-BAR/TGR5 IN BILE ACID-INDUCED ACTIVATION OF EPIDERMAL GROWTH FACTOR RECEPTOR AND MITOGEN-ACTIVATED PROTEIN KINASES IN GASTRIC CARCINOMA CELLS.
| Project/Area Number |
17590680
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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 | Showa University |
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Principal Investigator |
YASUDA Hiroshi Showa University, School of Medicine, Associate Professor, 医学部, 講師 (80262129)
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| Project Period (FY) |
2005 – 2006
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| Keywords | bile acids / EGF receptor / M-BAR / TGR5 / GPCR / ADAM |
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| Research Abstract |
Bile acids, which have been implicated in carcinogenesis of the gastrointestinal tract, share properties of tumor promoters in that both affect cell signal-transduction pathways responsible for cell proliferation. The results of several studies suggest that mitogen-activated protein kinase activation is involved in the cellular effects of bile acids. In the present study, we demonstrate that treatment of AGS human gastric carcinoma cells with bile acids results in activation of epidermal growth factor receptor (EGFR)-extracellular signal regulated kinase (ERK)1/2, which is also important for regulating cellular growth. Phosphoactivation of EGFR following treatment of cells with deoxycholate (DC) is ligand-dependent, since treatment of cells with heparin-binding EGF-like growth factor (HB-EGF) antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibited. Membrane-type bile acid receptor (M-BAR) BG37/TGR5 is a recently identified GPCR (G-protein-coupled receptor) for bile acids. Introduction of siRNAs that target M-BAR mRNA for degradation results in potent suppression of DC-induced phosphorylation of EGFR on tyrosine, as well as ERK1/2 activation, in AGS cells. Furthermore, pretreatment of cells with the metalloprotease inhibitor BiPS resulted in potent inhibition of DC-induced EGFR activation in AGS cells. Finally, introduction of siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced activation of EGFR and ERK1/2. These results lead us to conclude that bile acids transactivate EGFR through M-BAR-and ADAM/HB-EGF-dependent mechanisms in AGS cells. M-BAR, which may be involved in gastric carcinogenesis, could potentially serve as a target for cancer prevention.
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Research Products
(12 results)
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[Journal Article] Autocrine Loop between Transforming Growth Factor-β1 and Interleukin-1β through Smad3- and ERK-dependent Pathways in Rat Pancreatic Stellate Cells.2006
Author(s)
Aoki H, Ohnishi H, Hama K, Ishijima T, Satoh Y, Hanatsuka K, Ohashi A, Wada A, Miyata T, Kita H, Yamamoto H, Osawa H, Sato K, Tamada K, Yasuda H, Mashima H, Sugano K
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Journal Title
Am J Physiol Cell Physiol. 290
Pages: C1100-1108
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Autocrine Loop between Transforming Growth Factor-β1 and Interleukin-1β through Smad3-and ERK-dependent Pathways in Rat Pancreatic Stellate Cells.2006
Author(s)
Aoki H, Ohnishi H, Hama K, Ishijima T, Satoh Y, Hanatsuka K, Ohashi A, Wada A, Miyata T, Kita H, Yamamoto H, Osawa H, Sato K, Tamada K, Yasuda H, Mashima H, Sugano K.
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Journal Title
Am J Physiol Cell Physiol. 290
Pages: C1100-1108
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway.2006
Author(s)
Hama K, Ohnishi H, Aoki H, Kita H, Yamamoto H, Osawa H, Sato K, Tamada K, Mashima H, Yasuda H, Sugano K.
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Journal Title
3iochem Biophys Res Commun. 340
Pages: 742-50
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet.2005
Author(s)
Yoshikumi Y, Mashima H, Ueda N, Ohno H, Suzuki J, Tanaka S, Hayashi M, Sekine N, Ohnishi H, Yasuda H, liri T, Omata M, Fujita T, Kojima 1.
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Journal Title
J Cellular Biochem 95
Pages: 1157-1168
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Modified diagnostic criteria of drug-induced liver injury proposed by the international consensus meeting.2005
Author(s)
Iwasa M, Zeniya M, Kumagai T, Hisamochi A, Yasuda H, Nishiuchi M, Akisawa N, Mantani N, Watanabe M, Ito T, Nakamura A, Takikawa H, Adachi Y.
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Journal Title
Hepato-Gastroenterol. 52
Pages: 869-874
Description
「研究成果報告書概要(欧文)」より
