2005 Fiscal Year Final Research Report Summary
Establishment of the method for estimation of carcinogenetic risk in gastrointestinal adenomas using double transgenic mice
| Project/Area Number |
16590487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
HOMMA Sadamu The Jikei University School of Medicine, Assistant Professor, 医学部, 助教授 (50192323)
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| Project Period (FY) |
2004 – 2005
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| Keywords | APC gene / Familial Adenomatous Polyposis / Risk of carcinogenesis / LOH mutation / Model mice / Colorectal cancer |
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| Research Abstract |
Double transgenic cells with both reporter and repressor gene should be fully functional for establishment of the method for estimation of carcinogenetic risk using double transgenic mice. For this purpose, NIH-3T3 cells transduced with both LacZ reporter gene and LacZ represser gene were established. Expression of reporter gene by treatment of the cells with Chlorambutyl, inducer of large defect mutation of chromosomes, has been examined. APC gene knockout construct including reporter gene and Smad4 knockout construct including represser gene were now being generated using genomic DNA encoding APC gene and Smad4 gene for establishment of the double transgenic mice. APC gene knockout mice with different mutation site (APC1309,APC850Min,APC580D) were examined for number of gastrointestinal tumors and accumulation of beta-catenin into cytoplasm and nucleus. It was demonstrated that mice with large number of tumors showed high accumulation of beta-catenin. However, APC1309 mice exhibiting no beta-catenin accumulation showed tumor development, suggesting that pathway without association with beta-catenin might be involved in the tumorigenesis in APC gene knockout mice.
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