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2007 Fiscal Year Final Research Report Summary

An exhaustive study of tumorigenesis and development of a novel molecular targeting therapy for canine mastocytoma

Research Project

Project/Area Number 17208027
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

MATSUDA Hiroshi  Tokyo University of Agriculture and Technology, Graduate School, Institute of Symbiotic Science and Technology, Professor (80145820)

Co-Investigator(Kenkyū-buntansha) TANAKA Akane  Tokyo University of Agriculture and Technology, Graduate School, Institute of Symbiotic Science and Technology, Associate Professor (80418673)
SHIMODA Minoru  Tokyo University of Agriculture and Technology, Graduate School, Institute of Symbiotic Science and Technology, Professor (50154323)
ARAI Katsuhiko  Tokyo University of Agriculture and Technology, Faculty of Agriculture, Associate Professor (60175940)
TSUJIMOTO Hajime  University of Tokyo, Graduate School of Agricultureal and Life Sciences, Professor (60163804)
NISHIMURA Ryouhei  University of Tokyo, Graduate School of Agricultureal and Life Sciences, Professor (80172708)
Project Period (FY) 2005 – 2007
Keywordsveterinary medicine / cancer / signal transduction / gene
Research Abstract

1) c-kit gene mutations in clinical samples of dog mastocytoma were widely analyzed. Gene mutations (insertion, internal tandem duplication, and deletion) in the c-kit juxtamembrane domain were found in less than 12% of all cases ; however, c-kit gene in 88% cases was a wild type.
2) Although mutated c-kit gene was cloned and transfected into mock cells, neoplastic proliferation was not induced, indicating that the c-kit gene mutations may not the major inducer of mast cell tumor. We investigated the other candidates that may induce neoplastic proliferation of mast cells, and found that the over-expression of D-type cyclins and one of Bcl-2 family proteins Mcl-1. We also found that the low expression of one of BH3 family proteins Bim-1 and tumor suppressors p21, p27, and p53.
3) Transcription factors NF- κ B and AP-1 were found to be activated in neoplastic mast cells and by the addition of those transcription factor inhibitors into the culture, proliferation of neoplastic mast cells was abolished. Signaling molecules down below the PI3 kinase pathway, S6 kinase, was spontaneously activated and over-expression of S6 ribosomal protein was obvious.
4) We established a novel high-affinity IgE receptor-positive canine mast cell line with wild type c-kit receptors. By using cell lines and clinical samples, production of growth factors and cytokines in dog mastocytoma was analyzed and found auto-production of interleukin-3, and -6, GM-CSF, and SCF, and the expression of those receptors was found. Neutralization of those auto-produced cytokines by specific antibodies partially inhibited cell proliferation, indicating that, at least in part, auto-production of growth factors by mastocytoma cells themselves may induce cell proliferation and/or survival.

  • Research Products

    (11 results)

All 2008 2007 2005 Other

All Journal Article (7 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Establishment of a novel high-affinity IgE receptor-positive canine mast cell line with wild type c-kit receptors.2008

    • Author(s)
      Yosuke Amagai
    • Journal Title

      Biochem. Biophys. Res. Commun. 366

      Pages: 857-861

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Identification of c-kit mutations-independent neoplastic cell proliferation of canine mast cells.2008

    • Author(s)
      Keitaro Ohmori
    • Journal Title

      Vet. Immunol. Immunopathol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Establishment of a novel high-affinity IgE receptor-positive canine mast cell line with wild type c -kit receptors2008

    • Author(s)
      Yosuke, Amagai
    • Journal Title

      Biochem. Biophys. Res. Commun 366

      Pages: 857-861

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of c-kit mutations-independent neoplastic cell proliferation of canine mast cells.2008

    • Author(s)
      Keitaro, Ohmori
    • Journal Title

      Vet. Immunol. Immunopathol (In press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Therapeutic approaches for neoplastic disorders in companion animal : targeting therapy2007

    • Author(s)
      Akane, Tanaka
    • Journal Title

      Anitecs 19

      Pages: 25-31

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel NF-kappaB inhibitor,IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors.2005

    • Author(s)
      Akane Tanaka
    • Journal Title

      Blood 105

      Pages: 2324-2331

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A novel NF-kappaB inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c- kit receptors.2005

    • Author(s)
      Akane, Tanaka
    • Journal Title

      Blood 105

      Pages: 2324-2331

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Effect of a novel NF-KB inhibitor, IMD-0354, on human hematopoietic cell malignancies2005

    • Author(s)
      Hiroshi, Matsuda
    • Organizer
      34th Annual Scieitific Meeting of the International Society for Experimental Hematology
    • Place of Presentation
      Glasgow, Scotland
    • Year and Date
      20050000
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Effect of a novel NF-kB inhibitor, IMD-0354, on human hematopoietic cell malignancies2005

    • Author(s)
      Hiroshi Matsuda
    • Organizer
      34th Annual Scientific Meeting of the International Society for Experimental Hematology
    • Place of Presentation
      Glasgow, Scotland
    • Year and Date
      2005-07-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 伴侶動物の腫瘍治療:分子標的治療、アニテック2007

    • Author(s)
      田中あかね
    • Total Pages
      25-31
    • Publisher
      研成社
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.tuat.ac.jp/mol_path/

URL: 

Published: 2010-02-04  

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