2019 Fiscal Year Final Research Report
Determining the driver gene for colon carcinogenesis accelerated by chronic inflammation
| Project/Area Number |
17K08761
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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 |
Experimental pathology
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| Research Institution | Tottori University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 炎症発癌 / ドライバー遺伝子 / 大腸発癌 |
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| Outline of Final Research Achievements |
We investigated which genetic alterations observed in human colorectal carcinogenesis are critical in the inflammation-related bowel carcinogenesis. The inflammation was evoked by implantation of foreign substances such as plastic plate. Male mouse intestinal organoids with K-ras activation and APC knockdown were grew lethally in the inflammation formed in female nude mice. When an organoid obtained from a homozygous p53 gene-deficient mouse and implanted them into the inflammatory region, they formed fibrous tumors. Organoids obtained from a heterozygous p53 gene-deficient mouse, they did not grow under the inflammation. Organoid obtained from a p53 gene homozygous mouse with APC knockdown formed tumors in mice, however, the histological type were fibrous ones.
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| Free Research Field |
実験病理学
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| Academic Significance and Societal Importance of the Research Achievements |
慢性炎症による大腸発癌のdriver遺伝子として，p53遺伝子に加えてどの大腸癌関連遺伝子が，どのような組合せで，真の“癌腫発生に必要なdriver遺伝子”となるのかを決定する．これにより，大腸の炎症発癌に対する新規の治療・予防のための標的遺伝子を明らかにすることができる．今後の炎症性腸疾患に対する創薬研究開発等への波及効果が望める.
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