Nuclear IKKbeta regulates DEN-induced hepatic carcinogenesis through the suppression of DNA-binding activity of HNF4alpha
| Project/Area Number |
16K18419
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Hiroshima Jogakuin University (2017-2018)
Hiroshima University (2016) |
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Principal Investigator |
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| Research Collaborator |
KAMATA Hideaki 広島大学, 医歯薬保健学研究院, 准教授 (10233925)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肝炎 / 肝がん / 化学発がん / シトクロムp450 / IKKβ / HCC / DEN / HNF4 / IKK / 肝線維化 / 肝細胞死 |
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| Outline of Final Research Achievements |
Gene analysis revealed that expression of hepatic cytochrome P450 (CYP) enzymes including Cyp2E1, which mediates the activation of chemical carcinogens, was markedly reduced in Tg-IKKβΔhep. Injection of TNFα- or IL-1β in mice markedly suppress the expression of cyp genes in livers. Although HNF4α express normally in liver, its binding to the chromatin was prevented in livers in Tg-IKKβΔhep and mice injected with TNFα or IL-1β. These results suggest that suppression of Cyp2E1 expression reduced DEN induced hepatocarcinogenesis in inflammatory conditions.
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| Academic Significance and Societal Importance of the Research Achievements |
一般に炎症は発がんを亢進するが、逆に炎症による組織障害が化学発がんの抑制につながる新たなケースが本実験により示された。炎症による肝特異的転写因子HNF4αの活性抑制が、シトクロムp450などの代謝系遺伝子の発現抑制をもたらし、これが発がん抑制に至ることまで解明した。この研究成果は、炎症による発がん制御において新しい分子機構の解明につながるものであると考えられた。
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Report
(4 results)
Research Products
(6 results)
