| Project/Area Number |
26670391
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Chiba Cancer Center (Research Institute) |
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Principal Investigator |
Hippo Yoshitaka 千葉県がんセンター(研究所), 発がん制御研究部, 部長 (30359632)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵臓癌 / モデル / ３次元培養 / 発がん / 膵癌 / オルガノイド / Kras / 幹細胞 |
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| Outline of Final Research Achievements |
In the multistep carcinogenesis of pancreatic ductal adenocarcinoma (PDAC), activation of Kras is an initiating event in most cases, which is followed by inactivation of other highly mutated tumor suppressor genes (TSGs) such as p16, p53, or SMAD4. As we previously demonstrated that murine primary intestinal organoids could be transformed by suppression of Apc, we took a similar approach to model PDAC. We activated Kras by lentivirally introducing Cre in pancreatic organoids in 3-D culture, which resulted in development of small nodules containing a few atypical glands in nude mice. But solid tumors with invasive and dysplastic features were induced by transducing Kras-activated organoids with shRNAs against major TSGs, clearly indicating that in vivo microenvironment is indispensable for tumor development. This model would likely accelerate PDAC research in many aspects.
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