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

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09873
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Gunma 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
• Keywords: 遺伝子 / 遺伝性腫瘍 / 癌 / 骨格筋

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.

Free Research Field

内分泌

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。