Roles of BMP signaling in pancreatic cancer initiation and progression using a genetically-engineered mouse model
| Project/Area Number |
16K07110
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Ijichi Hideaki 東京大学, 医学部附属病院, 講師 (70463841)
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| Co-Investigator(Kenkyū-buntansha) |
伊佐山 浩通 順天堂大学, 医学部, 教授 (70376458)
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| Research Collaborator |
Miyabayashi Koji
Sano Makoto
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵癌 / BMPシグナル / BMP / BMPII型受容体 / acinar-ductal metaplasia / 細胞接着 |
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| Outline of Final Research Achievements |
Pancreatic cancer is one of the most deadly cancers. Understanding the underlying mechanisms of the disease formation is quite important. We have already established a mouse model containing pancreas epithelium-specific mutant Kras expression and TGF-beta type II receptor (Tgfbr2) knockout(Kras+Tgfbr2KO), which can recapitulate human disease very well. Others reported that Smad4 knockout in the same context with Kras activation developed cystic tumors, suggesting that the difference of BMP signaling might result in this phenotypic difference. Thus, we combined the Kras+Tgfbr2 KO with BMP type II receptor (Bmpr2) knockout. The Kras+Tgfbr2KO+Bmpr2KO resulted in non-cystic, pancreatic cancer close to the Kras+Tgfbr2KO, which indicates that Bmpr2 is dispensable for pancreatic cancer formation. The impact on the prognosis is now under investigation.
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| Academic Significance and Societal Importance of the Research Achievements |
癌の分子生物学的知見に基づく分子標的治療、免疫療法、個別化医療等の目覚ましい進歩に対し、膵癌は依然として5年生存率9％と最難治癌であり、かつ罹患数および癌死数が増加しており、膵癌の病態の理解と予後に寄与する治療の開発は喫緊の課題である。本研究では、臨床像に近い膵発癌モデルを用い、膵癌の発癌進展および生命予後におけるBMPシグナルの寄与を明らかにすることを目的としている。膵発癌モデルでは、ヒトで遺伝子異常の多いSmad4よりも遺伝子異常の稀なTgfbr2のノックアウトの方が通常型膵癌に近い腫瘍が形成され、その理由を含めて膵癌形成の機序を明らかにできる可能性があり、現在腫瘍組織の解析中である。
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Report
(3 results)
Research Products
(2 results)
