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2005 Fiscal Year Final Research Report Summary

Involvement of p38 MAPK signaling pathway in cancer therapy

Research Project

Project/Area Number 16590569
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionAsahikawa Medical College

Principal Investigator

TANNO Satoshi  Asahikawa Medical College, Department of General Medicine, Assistant Professor, 医学部, 講師 (30333686)

Co-Investigator(Kenkyū-buntansha) OKUMURA Toshikatsu  Asahikawa Medical College, Department of General Medicine, Professor, 医学部, 教授 (60281903)
Project Period (FY) 2004 – 2005
KeywordsGI cancer / pancreatic cancer / p38 MAPK / Anticancer agents / Gemcitabine / chemoresistance / acquired chemoresistance / COX-2
Research Abstract

It has been reported that p38 MAPK is activated by various extracellular stimuli, and involved in the mechanism of regulating cell survival and death. We have demonstrated that p38 MAPK is strongly activated by gemcitabine, an anticancer drug, and plays a significant role in gemcitabine-induced cell death in human cancer cells (Cancer Res 2004,Biochem Biophys Res Commun 2004,Anticancer Res 2005). We found that inhibition of p38 MAPK activation decreased the gemcitabine-induced cytotoxicity, indicating that p38 MAPK activation regulates gemcitabine sensitivity. To further investigate whether p38 MAPK is involved in the acquired chemoresistance induced by gemcitabine, we established various gemcitabine-resistant subclones of human pancreatic cancer cell lines, and investigated the activation of p38 MAPK. We found that p38 activation was decreased in the gemcitabine-resistant subclones compared with parental cells. Furthermore, we found that Src, non-receptor tyrosine kinase, was activated, and expression of COX-2 was increased in p38 MAPK-inactive resistant subclones compared with parental cells. These results suggest that activation of p38 MAPK signaling is necessary for gemcitabine-induced cell death in human pancreatic cancer cells. Based upon these results, we would suggest that molecules of p38 MAPK signaling pathways should be listed as novel targets for gemcitabine-based therapy.

  • Research Products

    (7 results)

All 2005 2004

All Journal Article (7 results)

  • [Journal Article] Involvement of MEK-ERK signaling pathway in the inhibition of cell growth by troglitazone in human pancreatic cancer cells.2005

    • Author(s)
      Motomura W, Tanno S, et al.
    • Journal Title

      Biochem Biophys Res Commun 332

      Pages: 89-94

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells.2005

    • Author(s)
      Koizumi K, Tanno S, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 3347-3353

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of MEK-ERK signaling pathway in the inhibition of cell growth by troglitazone in human pancreatic cancer cells2005

    • Author(s)
      Motomura W, Tanno S, et al.
    • Journal Title

      Biochem Biophys Res Commun 332

      Pages: 89-94

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of p38 mitogen-activated protein kinase in gemcitabine-induced apoptosis in human pancreatic cancer cells.2004

    • Author(s)
      Habiro A, Tanno S, et al.
    • Journal Title

      Biochem Biophys Res Commun 316

      Pages: 71-77

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Serine/threonine Kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance.2004

    • Author(s)
      Tanno S, et al.
    • Journal Title

      Cancer Res 64

      Pages: 3486-3490

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibition of cell invasion and morphological change by troglitazone in cultured human pancreatic cancer cells.2004

    • Author(s)
      Motomura W, et al.
    • Journal Title

      J Gastroenterol 39

      Pages: 461-468

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Serine/threonine Kinase AKT is frequently activated in human bile duct cancer and is associated with increased radio-resistance.2004

    • Author(s)
      Tanno S, et al.
    • Journal Title

      Cancer Res 64

      Pages: 3486-3490

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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