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Analysis of function of tumor suppressor gene MEN1 in non-endocrine tumor tissue.

Research Project

Project/Area Number 17K09873
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionGunma University

Principal Investigator

Ozawa Atsushi  群馬大学, 大学院保健学研究科, 教授 (10573496)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords遺伝子 / 遺伝性腫瘍 / 癌 / 骨格筋 / 腫瘍 / マウス / 糖代謝 / 多発性内分泌腫瘍症 / 耐糖能 / 内分泌 / 内分泌学 / 内分泌腫瘍 / 細胞・組織 / マイクロアレイ
Outline of Final Research Achievements

The causative gene MEN1 of multiple endocrine neoplasia type 1(MEN1) is considered to be a tumor suppressor gene, but the function of menin, a translation product of MEN1, in non-endocrine tissues has not been fully elucidated. The function of menin in skeletal muscle was analyzed. A cDNA microarray analysis using skeletal muscle of Men1 heterozygous mice revealed that the variation of glucose metabolism-related genes was larger than that of the wild type. We also confirmed that the expression level of menin fluctuates during the process of differentiation of C2C12 myoblast cells into myotubes. Immunoblotting analysis using the extracted protein of isolated skeletal muscle after insulin administration revealed that the deletion of menin affected the expression levels of multiple proteins related to glucose metabolism.

Academic Significance and Societal Importance of the Research Achievements

MEN1遺伝子および翻訳産物meninの機能として、これまで膵臓のインスリン分泌能獲得や肝臓での糖新生における役割についていくつかの報告があるが、今回の研究成果によって、骨格筋におけるmenin発現のhaploinsufficiencyが筋肉での糖代謝機構に直接的な影響を与えていることが初めて明らかとなった。内分泌腺腫瘍化における癌抑制蛋白としての機能以外に、膵内分泌細胞、肝臓、骨格筋という糖代謝ネットワークにおいてmeninが重要な役割を演じていることが判明し、今後研究を発展させることでmeninが糖尿病の病態を考察する上での新しい観点や、創薬のターゲットとなる可能性が示された。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (9 results) (of which Invited: 3 results)

  • [Journal Article] Transcriptional Regulation of the Angptl8 Gene by Hepatocyte Nuclear Factor-1 in the Murine Liver.2020

    • Author(s)
      Watanabe T, Ozawa A,Masuda S, Yoshino S, Ishida E, Kondo U, Horiguchi K,Isii S, Tomaru T Shibusawa N, Saito T, Yamada E, Nakajima Y, Matsumoto S, Katano-Toki A, Okada S, Satoh T, Yamada M.
    • Journal Title

      Scientific reports

      Volume: 10 Issue: 1 Pages: 9999-9999

    • DOI

      10.1038/s41598-020-66570-0

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 多発性内分泌腫瘍の病態生理と臨床像2020

    • Author(s)
      小澤厚志
    • Journal Title

      日本臨床

      Volume: 78巻増刊4 Pages: 841-847

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 間脳下垂体機能障害の診断と治療:疑わないと始まらない2020

    • Author(s)
      小澤厚志
    • Journal Title

      内科

      Volume: 126巻3号 Pages: 591-596

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity2020

    • Author(s)
      Okada J, Yamada E, Saito T, Yokoo H, Osaki A, Shimoda Y, Ozawa A, Nakajima Y, Pessin JE, Okada S, Yamada M.
    • Journal Title

      Molecules

      Volume: 25 Issue: 3 Pages: 9999-9999

    • DOI

      10.3390/molecules25030495

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of the KCNJ5 Gene by SF-1 in the Adrenal Cortex: Complete Genomic Organization and Promoter Function2020

    • Author(s)
      Nishikido A, Okamura T, Nakajima Y, Ishida E, Miyamoto T, Toki AK, Matsumoto S, Yoshino S, Horiguchi K, Saito T, Yamada E, Ozawa A, Shimoda Y, Oyama T, Yamada M.
    • Journal Title

      Mol Cell Endocrinol

      Volume: 501 Pages: 110657-110657

    • DOI

      10.1016/j.mce.2019.110657

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Central Hypothyroidism Related to Pituitary Adenomas: Low Incidence of Central Hypothyroidism in Patients With Acromegaly2019

    • Author(s)
      Takamizawa T, Horiguchi K, Nakajima Y, Okamura T, Ishida E, Matsumoto S, Yoshino S, Yamada E, Saitoh T, Ozawa A, Tosaka M, Yamada S, Yamada M.
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 104 Issue: 10 Pages: 4879-4888

    • DOI

      10.1210/jc.2019-00466

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 内分泌内科医から見たMEN1に伴うpNETの診療2021

    • Author(s)
      小澤厚志
    • Organizer
      第94回日本内分泌学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] MEN研究の最新の知見(シンポジウム)2019

    • Author(s)
      小澤厚志、山田正信
    • Organizer
      第25回日本家族性腫瘍学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] MEN研究の最新の知見2019

    • Author(s)
      小澤厚志、山田正信
    • Organizer
      第25回日本家族性腫瘍学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 膵神経内分泌腫瘍症モデルマウスの解析2018

    • Author(s)
      小澤厚志、渡邉琢也、近藤友里、岡村孝志、石田恵美、堀口和彦、松本俊一、吉野聡、中島康代、佐藤哲郎、山田正信
    • Organizer
      第45回日本神経内分泌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵内分泌腫瘍を発症するモデルマウスの解析2018

    • Author(s)
      小澤厚志、渡邉琢也、近藤友里、錦戸彩加、岡村孝志、石田恵美、堀口和彦、吉野聡、中島康代、石井角保、渋沢信行、佐藤哲郎、山田正信
    • Organizer
      第61回日本糖尿病学会年次学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵神経内分泌腫瘍症の2つのモデルマウスの解析2018

    • Author(s)
      小澤厚志、渡邉琢也、近藤友里、岡村孝志、石田恵美、堀口和彦、吉野聡、中島康代、石井角保、渋沢信行、佐藤哲郎、山田正信
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵神経内分泌腫瘍症の2つのモデルマウスの解析2018

    • Author(s)
      小澤厚志、渡邉琢也、近藤友里、岡村孝志、石田恵美、堀口和彦、吉野聡、中島康代、石井角保、渋沢信行、佐藤哲郎、山田正信
    • Organizer
      日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵内分泌腫瘍を発症するモデルマウスの解析2018

    • Author(s)
      小澤厚志、渡邉琢也、近藤友里、錦戸彩加、岡村孝志、石田恵美、堀口和彦、吉野聡、中島康代、石井角保、渋沢信行、佐藤哲郎、山田正信
    • Organizer
      日本糖尿病学会年次学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 癌抑制蛋白meninの膵ラ氏島細胞における機能解析2017

    • Author(s)
      小澤厚志、渡邉琢也、堀口和彦、松本俊一、吉野聡、中島康代、登丸琢也、石井角保、渋沢信行、岡田秀一、佐藤哲郎、山田正信
    • Organizer
      日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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