| Project/Area Number |
26293080
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
Niki Toshiro 自治医科大学, 医学部, 教授 (90198424)
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| Co-Investigator(Kenkyū-buntansha) |
佐久間 裕司 札幌医科大学, 医学部, 准教授 (10364514)
吉本 多一郎 自治医科大学, 医学部, 講師 (20634166)
松原 大祐 自治医科大学, 医学部, 准教授 (80415554)
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| Project Period (FY) |
2014-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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| Keywords | 肺腺癌 / 上皮間葉転換 / エピジェネティックス / 分化形質 / メチル化 / 肺癌 / エピジェネティクス |
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| Outline of Final Research Achievements |
About 20-30% of lung adenocarcinoma show loss of expression of TTF-1 (thyroid-specific transcription factor-1), a master regulator of lung development and differentiation. These adenocarcinomas frequently present with either mucinous or poorly differentiated solid morphology, features of epithelial-mesenchymal transition, and lack targetable driver mutations, such as EGFR and ALK. In this study, we have revealed that these characteristics of this subset of lung cancer may be causally related with 1) abnormalities of histone modifier expression, 2) loss of expression of chromatin remodelers BRG1/BRM, and inactivation of TTF-1 gene itself by gene mutation or methylation.
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| Academic Significance and Societal Importance of the Research Achievements |
ゲノム解析の進歩にも拘わらず、肺腺癌の20-30％では、治療標的となるドライバー変異がいまだ見出せていない。本研究によってもたらされた知見により、このような一群の肺腺癌におけるエピジェネティックス異常の重要性が認識され、今後の診断・治療開発に向けた研究が促進されることが期待される。
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