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Involvement of the melanocortin receptor pathway in pancreatic and colorectal carcinogenesis and its application to cancer prevention

Research Project

Project/Area Number 25290049
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Takahashi Mami  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (90214973)

Co-Investigator(Kenkyū-buntansha) MUTOH Michihiro  国立研究開発法人 国立がん研究センター, 社会と健康研究センター 予防研究部 予防研究室, 室長 (30392335)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsメラノコルチン受容体 / 膵臓がん / 大腸がん / がん予防 / アグーチ
Outline of Final Research Achievements

The Ay allele promoted pancreatic carcinogenesis in Ptf1a-KrasG12D mice and azoxymethane (AOM)-induced colorectal carcinogenesis in diabetic KK mice. Increased expression of CSF1 and accumulation of macrophages was observed in pancreatic carcinoma tissues in Ptf1a-KrasG12D-Ay mice and AOM-induced colorectal carcinoma tissues in KK-Ay mice. The agouti overexpression in pancreatic cancer cell lines established from Ptf1a-KrasG12D mice increases the expression of adipogenesis-related gene X via antagonizing MCRs. The gene X product significantly elevated CSF1 expression. Expression of the gene X was decreased by treatment with forskolin, which elevates intracellular cAMP and stimulates downstream pathways of MCRs. However, effects of forskolin on inflammatory factors were different among cell lines and the effects on carcinogenesis was supposed to be not consistent.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (9 results)

All 2016 2014 2013 Other

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

  • [Journal Article] Possible involvement of pancreatic fatty infiltration in pancreatic carcinogenesis.2016

    • Author(s)
      Hori, M., Mutoh, M., Imai, T., Nakagama, H., Takahashi, M.
    • Journal Title

      Journal of the Pancreas

      Volume: 17 Pages: 166-175

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A^y allele promotes azoxymethane-induced colorectal carcinogenesis via macrophage migration in hyperlipidemic/diabetic KK mice.2013

    • Author(s)
      Ito, K., Ishigamori, R., Mutoh, M., Ohta, T., Imai, T., Takahashi, M
    • Journal Title

      Cancer Sci.

      Volume: (in press) Issue: 7 Pages: 835-843

    • DOI

      10.1111/cas.12162

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Increase of pancreatic cancer development in pancreas-specific K-ras mutant mice by crossing with obesity Ay mice and involvement of the M-CSF.2016

    • Author(s)
      Takahashi, M.,Ishigamori, R.,Mutoh, M., Fujii, G., Miyamoto, S., Imai, T.
    • Organizer
      Tenth AACR-JCA Joint Conference
    • Place of Presentation
      米国ハワイ州
    • Year and Date
      2016-02-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Agoutiによるマウス膵臓発がん促進メカニズム2014

    • Author(s)
      高橋真美、石ヶ守里加子、藤井元、武藤倫弘、今井俊夫
    • Organizer
      第73回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] マウス膵臓発がんモデルにおけるAyアレルによる発がん促進とそのメカニズム2014

    • Author(s)
      高橋真美、石ヶ守里加子、藤井元、武藤倫弘、今井俊夫
    • Organizer
      NCC-NCGM合同リトリート
    • Place of Presentation
      常総
    • Year and Date
      2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] アゾキシメタン誘発大腸発がん高感受性のII型糖尿病モデルマウスにおけるAyアレルによる腫瘍形成促進

    • Author(s)
      高橋真美、伊藤久美子、石ヶ守里加子、中西るり、武藤倫弘、藤井元、太田敏博、今井俊夫
    • Organizer
      第20回日本がん予防学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス膵臓発がんにおけるAyアレルによる発がん促進

    • Author(s)
      高橋真美、石ヶ守里加子、武藤倫弘、田中卓二、今井俊夫
    • Organizer
      第28回発癌病理研究会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report
  • [Presentation] Ayアレルによる膵臓発がん及び大腸発がんの促進におけるマクロファージコロニー刺激因子の関与

    • Author(s)
      高橋真美、石ヶ守里加子、中西るり、尾沼若奈、小宮雅美、藤井元、武藤倫弘、田中卓二、今井俊夫
    • Organizer
      第24回日本消化器癌発生学会
    • Place of Presentation
      金沢
    • Related Report
      2013 Annual Research Report
  • [Presentation] Ayアレルによるマウス膵臓発がん促進におけるM-CSFの関与

    • Author(s)
      高橋真美、石ヶ守里加子、尾沼若奈、小宮雅美、藤井元、武藤倫弘、田中卓二、今井俊夫
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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