2017 Fiscal Year Final Research Report
Notch Signaling regulates the development of hepatocelular carcinoma.
| Project/Area Number |
16K19369
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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 |
Gastroenterology
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| Research Institution | Tokai University |
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Principal Investigator |
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| Research Collaborator |
INAGAKI Yutaka
HOZUMI Katsuto
KAMIYA Akihide
SUMIYOSHI Hideaki
MIKAMI Kenichiro
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | Notch / Notchリガンド / 肝細胞癌 / 肝再生 / 肝線維化 |
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| Outline of Final Research Achievements |
In the present study, we investigated how differential Notch signaling modulates hepatic carcinogenesis using Jag1 conditional knockout mice. Hepatocellular carcinoma (HCC) was induced in Jag1-floxed (control) and Mx-Cre/Jag1-floxed mice (Jag1 cKO) by diethylnitrosamine (DEN) treatment.
In this results, the incidence of HCC occurrence was significantly increased in Jag1 cKO mice compared to that in the control animals. Consistent with this finding, gene expression of Dll4 was increased in cancerous tissues in parallel to the Hes1 (a downstream target gene of Notch signaling) expression levels. In addition, the signaling switch from Jag1/Notch2 to Dll4/Notch3 was observed in the peripheral region of HCC nodules, where cancer cells were stained positively for Ki67, a cell-proliferation marker.
These results suggest that HCC development is promoted by a signaling switch from Jag1/Notch2 to Dll4/Notch3, and that Dll4/Notch3 signaling could be a potential target to suppress HCC development.
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| Free Research Field |
発生生物学
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