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2007 Fiscal Year Final Research Report Summary

Research on premalignant lesions using beta-catenin/Tcfreporter mice

Research Project

Project/Area Number 17390112
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionGifu University

Principal Investigator

MORI Hideki  Gifu University, Graduate School of Medicine, Professor (70021433)

Co-Investigator(Kenkyū-buntansha) YAMADA Yasuhiro  Gifu University, Graduate School of Medicine, Lecturer (70313872)
HIROSE Yoshinobu  Gifu University, Hospital, Associate professor (20293574)
MATSUNAGA Kengo  Gifu University, Hospital, Assistant professor (00402173)
Project Period (FY) 2005 – 2007
Keywordsbeta-catenin / tcf / gastric cancer / colon cancer / premalignant lesion
Research Abstract

Apc ^(min/+) mouse, a mouse model for human familial adenomatosis polyposis (FAP), contains a truncating mutation in the Apc gene and spontaneously develops intestinal tumors. Our previous study revealed two distinct stages of tumorigenesis in the colon of Apc^<Min/+> mouse ; microadenomas and macroscopic tumors. Microadenomas already have lost their remaining allele of the Apc and all microadenomas show accumulation of β-catenin, indicating that activation of the canonical Wnt pathway is an initiating event in the tumorigenesis. This study shows that expression of nuclear β-catenin in macroscopic tumors is further upregulated in comparison with that in microadenomas. Furthermore, transcriptional activity of β-catenin/T-cell factor (Tcf) signaling, assessed using β-catenin/Tcf reporter transgenic mice is higher in the macroscopic tumors than that in microadenomas. In addition, the expression level of Dickkopf-1 (Dick1), which is known to be a negative modifier of the canonical Wnt pathway, was reduced only in colon tumors. These results suggest that activation of β-catenin/Tcf transcription plays a role, not only in the initiation stage, but also in the promotion stage of colon carcinogenesis in Apc ^(Min/+) mice. We further demonstrated that the gastric tumors developed in Apc^(Mini/+) mice express higher β-catenin/Tcf transcriptions, thus suggesting that the canonical Wnt signaling is involved in gastric carcinogenesis as well.

  • Research Products

    (12 results)

All 2008 2007

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Further upregulation of beta-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of ApcMin/+ mice.2008

    • Author(s)
      Oyama T, et. al.
    • Journal Title

      Carcinogenesis

      Pages: 666-672

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Development of gastric tumors in Apc Min/+ mice by the activation of the β-catenin/Tcf signaling pathway.2007

    • Author(s)
      Tomita H, et. al.
    • Journal Title

      Cancer Res. 67

      Pages: 4079-87

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Modifying effect of dietary sesaminol glucosides on the formation of azoxymethane-induced premalignant lesions of rat colon.2007

    • Author(s)
      Sheng HQ, et. al.
    • Journal Title

      Cancer Lett. 246

      Pages: 63-68

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells.2007

    • Author(s)
      Oka N, et. al.
    • Journal Title

      Biochem Biophys Res Commun 360

      Pages: 553-559

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Development of gastric tumors in Apc Min/+ mice by the activation of the β-catenin/Tcf signaling pathway2007

    • Author(s)
      Tomita, H., et. al.
    • Journal Title

      Cancer Res 67

      Pages: 4079-87

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Modifying effect of dietary sesaminol glucosides on the formation of azoxymethane-induced premalignant lesions of rat colon2007

    • Author(s)
      Sheng, HQ., et. al.
    • Journal Title

      Cancer Lett 246

      Pages: 63-68

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells2007

    • Author(s)
      Oka, N., et. al.
    • Journal Title

      Biochem Biophys Res Commun 360

      Pages: 553-559

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Precancerous conditions of the colon ; ultistage carcinogenesis in animal models A review. In Precancerous condition : new research2007

    • Author(s)
      Mori, H., et. al.
    • Journal Title

      Nova Science Publishers, Inc (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Further upregulation of β-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of Apc Min/+ mice2007

    • Author(s)
      Oyama, T., et. al.
    • Journal Title

      Carcinogenesis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Multistep carcinogenesis of the colon in Apc Min mouse2007

    • Author(s)
      Yamada Y, et. al.
    • Organizer
      The 38th International Symposium of The Princess Takamatsu Cancer Research Fund
    • Place of Presentation
      パレスホテル
    • Year and Date
      2007-11-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Multistep carcinogenesis of the colon in Ape Min mouse2007

    • Author(s)
      Yamada, Y., et. al.
    • Organizer
      The 38th International Symposium of The Princess Takamatsu Cancer Research Fund
    • Place of Presentation
      Palace Hotel, Tokyo
    • Year and Date
      2007-11-27
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Precancerous conditions of the colon; multistage carcinogenesis in animalmodels A review.In Precancerous condition: new research.2007

    • Author(s)
      Mori H, et. al.
    • Publisher
      Nova Science Publishers, Inc., (In press)
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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