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 |
Research Field |
Gastroenterology
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Research Institution | Tokai University |
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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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | Notch / Notchリガンド / 肝細胞癌 / 肝再生 / 肝線維化 / 肝癌 / 癌関連線維芽細胞 / Jag1 / Dll4 / Notch受容体 / 再生医学 / 癌 / 発生・分化 / 幹細胞 / Notchシグナル |
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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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Identification of a novel alpha-fetoprotein- expressing cell population induced by Jagged1/Notch2 signal in murine fibrotic liver.2017
Author(s)
Yasuhiro Nakano, Sachie Nakao, Hideaki Sumiyoshi, Kenichiro Mikami, Yuri Tanno, Minako Sueoka, Daigo Kasahara, Hiroshi Kimura, Tadashi Moro, Akihide Kamiya, Katsuto Hozumi, Yutaka Inagaki
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Journal Title
Hepatol Commun
Volume: 印刷中
Issue: 3
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Jagged1/Notchシグナルを介した線維肝再生における前駆細胞動員機構の解明2017
Author(s)
中野 泰博, 中尾 祥絵, 住吉 秀明, 三上 健一郎, 丹野 友里, 末岡 美那子, 笠原 大瑚, 木村 啓志, 茂呂 忠, 紙谷 聡英, 穂積 勝人, 稲垣 豊
Organizer
第16回 日本再生医療学会 総会
Place of Presentation
仙台国際センター(宮城県・仙台市)
Year and Date
2017-03-07
Related Report
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[Presentation] Jagged1/Notchシグナルは線維肝再生における肝前駆細胞の動員に機能する2016
Author(s)
中野 泰博, 中尾 祥絵, 住吉 秀明, 三上 健一郎, 丹野 友里, 末岡 美那子, 笠原 大瑚, 木村 啓志, 茂呂 忠, 紙谷 聡英, 穂積 勝人, 稲垣 豊
Organizer
第39回 日本分子生物学会 年会
Place of Presentation
パシフィコ横浜(神奈川県・横浜市)
Year and Date
2016-11-30
Related Report
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[Presentation] Contribution of Jagged1/Notch Signaling to Murine Fibrotic Liver Regeneration through Possible Dedifferentiation of Mature Hepatocytes2016
Author(s)
Yasuhiro Nakano, Sachie Nakao, Hideaki Sumiyoshi, Kenichiro Mikami, Yuri Tanno, Daigo Kasahara, Hiroshi Kimura, Tadashi Moro, Akihide Kamiya, Katsuto Hozumi, Yutaka Inagaki
Organizer
American Association for the Study of Liver Diseases - Liver meeting
Place of Presentation
ボストン(アメリカ合衆国)
Year and Date
2016-11-11
Related Report
Int'l Joint Research
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