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2018 Fiscal Year Final Research Report

Roles of BMP signaling in pancreatic cancer initiation and progression using a genetically-engineered mouse model

Research Project

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Project/Area Number 16K07110
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

Ijichi Hideaki  東京大学, 医学部附属病院, 講師 (70463841)

Co-Investigator(Kenkyū-buntansha) 伊佐山 浩通  順天堂大学, 医学部, 教授 (70376458)
Research Collaborator Miyabayashi Koji  
Sano Makoto  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords膵癌 / BMPシグナル
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.

Free Research Field

膵癌、消化器内科学

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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Published: 2020-03-30   Modified: 2020-07-01  

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