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Establishment of novel gastric cancer mouse models

Research Project

Project/Area Number 16K07111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionKanazawa University

Principal Investigator

Oshima Hiroko  金沢大学, がん進展制御研究所, 准教授 (80362515)

Research Collaborator Ida Miyuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胃がん / 悪性化 / マウスモデル / 炎症とがん
Outline of Final Research Achievements

In this project, we tried to establish a new mouse model for gastric cancer with metastasis using Gan mice together with conditional gene knockout mice. First we constructed CreER expressing mice in the gastric mucosa using Claudin2 and Claudin18 promoter. Claudin2 expresses in the inflamed gastric epitherial cells and Claudin18 expresses in the normal gastric epithelia. Then, we crossed Gan mice that develop gastric tumors and Tgfbr2 conditional KO mice or p53 conditional KO mice together with Cldn18-CreERT2 mice. And these mice were treated with Tamoxifen. However, disruption of Tgfbr2 gene and additional p53 gene mutation did not cause any morphological changes or invasion phenotype of gastric tumors of Gan mice. These results indicate that TGF beta signaling and p53 mutation are not sufficient for gastric tumor malignant progression.

Academic Significance and Societal Importance of the Research Achievements

胃がんは、日本人で罹患率の高いがんであるため、胃がんの悪性化を模倣するマウスモデルの開発は、胃がんの死亡率の克服のために重要な課題である。今回の研究で、新規悪性化胃がんモデルマウスの開発には至らなかったが、大腸がんと異なり、TGF-beta遮断や変異型p53発現だけでは悪性化に至らないことを個体レベルで証明した。現在、胃がん悪性化に関与が示唆される遺伝子である、K-rasの変異を導入するマウスとの交配を行っている。また、炎症反応特異的に発現するCldn2遺伝子プロモーターを使ったCre発現マウスによって、炎症反応特異的にがん関連遺伝子を発現させることにより、悪性化マウスモデル開発が期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (5 results)

  • [Journal Article] Stat3 is indispensable for damage-induced crypt regeneration but not for Wnt-driven intestinal tumorigenesis.2018

    • Author(s)
      Oshima H, Kok SY, Nakayama M, Murakami K, Voon DC, Kimura T, Oshima M
    • Journal Title

      FASEB J.

      Volume: 33 Issue: 2 Pages: 1873-1886

    • DOI

      10.1096/fj.201801176r

    • NAID

      120006621946

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined mutation of Apc, Kras and Tgfbr2 effectively drives metastasis of intestinal cancer.2018

    • Author(s)
      Sakai E, Nakayama M, Oshima H, Kouyama Y, Niida A, Fujii S, Ochiai A, Nakayama KI, Minori K, Suzuki Y, Hong CP, Ock CY, Kim SJ, Oshima M.
    • Journal Title

      Cancer Res.

      Volume: 78 Issue: 5 Pages: 1334-1346

    • DOI

      10.1158/0008-5472.can-17-3303

    • NAID

      120006452378

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.2017

    • Author(s)
      Nakayama M, Sakai K, Echizen K, Yamada Y, Oshima H, Han TS, Ohki R, Fujii S, Ochiai A, Robine S, Voon DC, Tanaka T, Taketo MM, Oshima M.
    • Journal Title

      Oncogene

      Volume: 36 Issue: 42 Pages: 5885-5896

    • DOI

      10.1038/onc.2017.194

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach2017

    • Author(s)
      Kimura Y, Ikuta K, Kimura T, Chiba T, Oshima H, Oshima M, *Nishi E, *Seno H
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 43052-43052

    • DOI

      10.1038/srep43052

    • NAID

      120006355734

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Myeloid Differentiation Factor 88 Signaling in Bone Marrow-Derived Cells Promotes Gastric Tumorigenesis by Generation of Inflammatory Microenvironment.2016

    • Author(s)
      Maeda Y, Echizen K, Oshima H, Yu L, Sakulsak N, Hirose O, Yamada Y, Taniguchi T, Jenkins BJ, Saya H, Oshima M.
    • Journal Title

      Cancer prevention research

      Volume: 9 Issue: 3 Pages: 253-263

    • DOI

      10.1158/1940-6207.capr-15-0315

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells.2016

    • Author(s)
      Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 2 Pages: 140-148

    • DOI

      10.1111/cas.12849

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] がん転移における遺伝的多様性の役割2019

    • Author(s)
      大島浩子
    • Organizer
      第1回日本遺伝学会春季分科会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Stat3 activation is indispensable for mucosal regeneration but not for Wnt-driven tumorigenesis.2018

    • Author(s)
      Hiroko Oshima
    • Organizer
      9th General Assembly and International Conference of Asian Pacific Organization for Cancer Prevention (APOCP)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stat3 is requires for intestinal regeneration but not for Wnt-driven tumorigenesis.2018

    • Author(s)
      Hiroko Oshima
    • Organizer
      37th Sapporo International Cancer Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inflammatory microenvironment induces invasive colon cancer in the TGF-β suppressed epithelia.2017

    • Author(s)
      Oshima H, Nakayama M, Oshima M.
    • Organizer
      The 19th Takeda Science Foundation Symposium on Bioscience “Chronic Inflammation”.
    • Place of Presentation
      武田薬品研修所(大阪)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Critical role of Stat3 in intestinal regeneration but not in Wnt-activated tumorigenesis2017

    • Author(s)
      Hiroko Oshima, Eri Sakai, Mizuho Nakayama, Masanobu Oshima
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inflammatory microenvironment induces invasive colon cancer in the TGF-β suppressed epithelia2017

    • Author(s)
      Hiroko Oshima, Mizuho Nakayama, Masanobu Oshima
    • Organizer
      The 19th Takeda Science Foundation Symposium on Bioscience
    • Related Report
      2017 Research-status Report
  • [Presentation] Chronic inflammation and Stat3 in intestinal tumorigenesis.2016

    • Author(s)
      Oshima H, Nakayama M, Oshima M.
    • Organizer
      第75回日本癌学会学術総会(招待講演)
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] Bio Clinica2017

    • Author(s)
      大島浩子、大島正伸
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2017 Research-status Report
  • [Book] リンパ学2017

    • Author(s)
      大島浩子、越前佳奈恵、中山瑞穂、大島正伸
    • Total Pages
      5
    • Publisher
      日本リンパ学会
    • Related Report
      2017 Research-status Report
  • [Book] 特集 胃癌2017

    • Author(s)
      大島浩子、越前佳奈恵、中山瑞穂、大島正伸
    • Total Pages
      6
    • Publisher
      日本臨床社
    • Related Report
      2017 Research-status Report
  • [Book] 遺伝子変異と微小環境の相互作用による発がん。実験医学2016

    • Author(s)
      大島浩子,越前佳奈恵,大島正伸.
    • Total Pages
      139
    • Publisher
      羊土社
    • Related Report
      2016 Research-status Report
  • [Book] 慢性炎症と発がん2016

    • Author(s)
      大島浩子、大島正伸
    • Total Pages
      197
    • Publisher
      最新医学社
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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