| Project/Area Number |
17K08650
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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 | The University of Tokyo |
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Principal Investigator |
Kubota Yuji 東京大学, 医科学研究所, 助教 (70614973)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | がん / MAPK経路 / ERK経路 / シグナル伝達 / 再発癌 / 抗癌剤抵抗性 |
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| Outline of Final Research Achievements |
The ERK pathway (Raf-MEK-ERK) is activated by mitogenic stimuli and mediates proliferative and pro-survival signals. Somatic mutations in this pathway are frequently found in various cancers, and most of these oncogenes, such as EGFR, Ras and Raf, induce abnormal activation of ERK. However, the detailed molecular mechanism of the process by which they cause carcinogenesis. In this study, I performed global gene expression analysis of human cell-lines with high ERK activity and found that the oncogene-induced strong and constitutive ERK activation increases the expression of proteins and non-coding RNAs that promote carcinogenesis or acquired anticancer drug resistance.
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| Academic Significance and Societal Importance of the Research Achievements |
ERK経路を構成する遺伝子の多くは様々な癌で高率に変異が認められる。その多くはERKシグナルを異常活性化して癌化や抗癌剤抵抗性を誘導するが、その分子的基盤は不明な点が多かった。本研究により、癌遺伝子に由来する強力なERKシグナル下流において、発癌および抗癌剤抵抗性の獲得に寄与する様々な遺伝子とその機能が明らかにされた。これらの知見は新たな分子標的や癌治療法の開発を促進すると期待される。
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