| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Outline of Final Research Achievements |
We have previously demonstrated that multi-step intestinal tumorigenesis can be recapitulated by lentivirally introducing genetic aberrations into murine intesitnal organoids. By using this cell-based model, we aimed at elucidation of molecular mechanisms underlying colon carcinogenesis. Specifically, we isolated small intestines from conditional knockout or knock-in mice for Apc and mutant Kras, respectively, and transduced organoids with Cre-recombinase to achieve in vitro recombination. We investigated if RNAi-mediated inactivation of genes frequently mutated in colon cancer could cooperate towards tumorigenesis with Apc loss or Kras activation, by inoculating transduced oragnoids in dorsal skin of immunodeficient mice, and gained new insights into impacts of these genes. We also administered food-borne carcinogens to organoids, to see environmental factors could indeed affect tumorigenesis. These observations would likely highlight the relevance of this new model.
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