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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.

Research Project

Project/Area Number 17590680
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionShowa University

Principal Investigator

YASUDA Hiroshi  Showa University, School of Medicine, Associate Professor, 医学部, 講師 (80262129)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsbile acids / EGF receptor / M-BAR / TGR5 / GPCR / ADAM
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.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 2005

All Journal Article (17 results)

  • [Journal Article] 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.2007

    • Author(s)
      Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 154-159

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 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.2007

    • Author(s)
      Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M.
    • Journal Title

      3iochem Biophys Res Commun 354

      Pages: 154-159

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 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.2007

    • Author(s)
      Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M.
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 154-159

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Acute necrotizing esophagitis : role of nonsteroidal anti-inflammatory drugs.2006

    • Author(s)
      Yasuda H, Yamada M, Endo Y, Inoue K, Yoshiba M
    • Journal Title

      J Gastroenterol 42

      Pages: 2742-2746

    • NAID

      10017477135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regions in the G Protein γ Subunit Important for Interaction with Receptors and Effectors.2006

    • Author(s)
      Myung CS, Lim WK, Defilippo J, Yasuda H, Neubig R, Garrison JC
    • Journal Title

      Mol Pharmacol 69

      Pages: 877-887

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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
    • Journal Title

      Am J Physiol Cell Physiol. 290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [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.
    • Journal Title

      Am J Physiol Cell Physiol. 290

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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.
    • Journal Title

      3iochem Biophys Res Commun. 340

      Pages: 742-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regions in the G Protein γ Subunit Important for Interaction with Receptors and Effectors.2006

    • Author(s)
      Myung CS, Lim WK, Defilippo J, Yasuda H, Neubig R, Garrison JC.
    • Journal Title

      Mol Pharmacol. 69

      Pages: 877-887

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Acute necrotizing esophagitis : role of nonsteroidal anti-inflammatory drugs.2006

    • Author(s)
      Yasuda H, Yamada M, Endo Y, Inoue K, Yoshiba M.
    • Journal Title

      J Gastroenterol 42

      Pages: 2742-2746

    • NAID

      10017477135

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Regions in the G Protein γ Subunit Important for Interaction with Receptors and Effectors.2006

    • Author(s)
      Myung CS, Lim WK, Defilippo J, Yasuda H, Neubig R, Garrison JC.
    • Journal Title

      Mol Pharmacol 69

      Pages: 877-887

    • Related Report
      2006 Annual Research Report
  • [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
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 742-750

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the gastric pylorus.2005

    • Author(s)
      Yasuda H, Yamada M, Endo Y, Inoue K, Yoshiba M.
    • Journal Title

      J Gastroenterol 40

      Pages: 690-697

    • NAID

      10016671612

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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.
    • Journal Title

      J Cellular Biochem 95

      Pages: 1157-1168

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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.
    • Journal Title

      Hepato-Gastroenterol. 52

      Pages: 869-874

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the gastric pylorus.2005

    • Author(s)
      Yasuda H, Yamada M, Endo Y, Inoue K, Yoshiba M.
    • Journal Title

      Journal of Gastrotenterology 40

      Pages: 690-697

    • NAID

      10016671612

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway.2005

    • Author(s)
      Hama K, Ohnishi H, Aoki H, Kita H, Yamamoto H, Osawa H, Sato K, Tamada K, Mashima H, Yasuda H, Sugano K.
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 742-750

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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