Analysis of function of tumor suppressor gene MEN1 in non-endocrine tumor tissue.
| Project/Area Number |
17K09873
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Gunma University |
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Principal Investigator |
Ozawa Atsushi 群馬大学, 大学院保健学研究科, 教授 (10573496)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(15 results)
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[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.
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Journal Title
Scientific reports
Volume: 10
Issue: 1
Pages: 9999-9999
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Molecules
Volume: 25
Issue: 3
Pages: 9999-9999
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Mol Cell Endocrinol
Volume: 501
Pages: 110657-110657
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
J Clin Endocrinol Metab
Volume: 104
Issue: 10
Pages: 4879-4888
DOI
Related Report
Peer Reviewed
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