2022 Fiscal Year Final Research Report
The analysis of the functional role of Kras and canonical Wnt pathways for tumorigenesis of biliary system.
Project/Area Number |
21K20801
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0901:Oncology and related fields
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Research Institution | Kyoto University |
Principal Investigator |
Nagao Munemasa 京都大学, 医学研究科, 客員研究員 (20907860)
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Project Period (FY) |
2021-08-30 – 2023-03-31
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Keywords | 胆道癌 / 胆道腫瘍 / Wnt / Kras |
Outline of Final Research Achievements |
We revealed that the Hnf1bCreER mouse is a suitable CreER mouse line for genetic manipulation in the extrahepatic biliary tract epithelium including the EHBD and GB for the first time. In mice, concurrent activation of Kras and Wnt pathways induced biliary neoplasms including ICPN and BilIN. The biliary neoplasm spheroids were established and these neoplasm spheroids were subcutaneously into NOD/SCID mice. The xenograft analysis showed that ICPN and BilIN were putative precursors to invasive biliary cancer. Mechanistically, c-Myc contributed to tumorigenesis, whereas the Tgfb pathway inhibited it. These results were reported.
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Free Research Field |
胆道腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
これまで世界的にも胆道腫瘍マウスモデルはほとんど報告されていなかった。我々は研究期間を通じて、胆道上皮特異的に遺伝子改変ができる遺伝子改変マウスを発見し、Kras、Wntシグナルが胆道腫瘍を発生させるメカニズムを解析し、研究結果を報告した。これらの研究手法は胆道上皮における他の分子の機能的役割について解析することに応用ができるという点では非常に意義が大きいと考える。
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