Molecular mechanism of tumor progression by the regulation of glucose and lipid metabolism
| Project/Area Number |
17K08672
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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 |
Pathological medical chemistry
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉田 清嗣 東京慈恵会医科大学, 医学部, 教授 (70345312)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 癌 / 脂質代謝 / リン酸化酵素 / 脂質 |
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| Outline of Final Research Achievements |
We have previously shown that dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) exerts anti-tumor effects in various cancer cells. However, physiological function of Dyrk2 in mice largely unknown.
In this study, we first present that the expression of PPAR gamma, a key regulatory gene of lipid metabolism, was increased in DYRK2-knockdown MDA-MB-468 cells but not MCF7 cells. This finding suggests that DYRK2 may regulate the expression level of PPAR gamma in a subtype-dependent manner. We next investigate the phenotypes of Dyrk2-deficient mice. Dyrk2-deficient mice exhibited sudden death soon after birth due to respiratory failure. Furthermore, Dyrk2-deficient mice were found to show developmental abnormalities and congenital malformations of multiple organs. Taken together, we demonstrated that Dyrk2 is essential for embryonic development and provide a basis for improving our understanding of embryonic development and refractory pediatric disease.
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| Academic Significance and Societal Importance of the Research Achievements |
DYRK2は多数の癌において癌抑制因子として機能することがわかっている重要な分子である。しかしながら、DYRK2のマウス個体レベルでの生理的意義は全く不明である。本研究では、Dyrk2欠損マウスを作製し解析を行った。研究成果として、Dyrk2欠損マウスは、上気道を含む呼吸器の形成異常による呼吸不全を引き起こし、出生直後致死となることがわかった。また、Dyrk2欠損マウスは、多くの組織形成異常の表現型を示した。以上のことから、Dyrk2はマウスの生存に必須であり、Dyrk2欠損マウスが先天性奇形症候群の病態を解明する有用なモデルとなる可能性が示唆され、今後更なる研究が期待される。
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Report
(5 results)
Research Products
(5 results)
