1995 Fiscal Year Final Research Report Summary
Genetic Alterations Involved in Mouse Colon Tumorgenesis : Comparison between DMH-induced tumors and Spontaneous Tumors
| Project/Area Number |
06670248
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
OKAMOTO Mieko The Tokyo Metropolitan Institute of Medical Science. Department of Laboratory Animal Science, Researcher, 実験動物研究部門, 研究員 (80152354)
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| Project Period (FY) |
1994 – 1995
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| Keywords | mouse colon tumor / dimethylhydrazine / Multiple intestinal neoplasia (Min) / p53 gene / APC gene / ras genes / microsatellite instability / PCR-SSLP |
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| Research Abstract |
Genetic alterations in spontaneous tumors arising in F1 hybrid mice carring a Min mutation (nonsense mutation in the mouse APC gene) were compared with those in DMH-induced colon tumors developed in F1 hybrids without Min mutation. Tumors in Min mice were developed mainly in the small intestine, and less frequently in the colon.
PCR-SSCP analysis revealed that the vast maiority of the tumors in Min mice had lost their wild-type allele of the APC gene. PCR-SSLP nalysis with markers linked to the APC locus, suggested that allele loss at the APC locus seemed to be inferquent in DMH-induced tumors. Point mutations within the gene were detected in these tumors.
In contrast to the APC gene, neither LOH nor point mutations of the p53 gene were observed in spontaneous tumors in Min mice. DMH-induced tumors showed point mutations and LOH in the p53 gene, although their frequencies being much lower than those in human colon cancers. These data strongly suggest that p53 inactivation is not esential in mouse colon tumorgenesis. Tumors in Min mice showed no point mutations in the K-, H-, and N-ras genes.
PCR-SSLP analyzes with randomly selected markers revealed that microsatellite instability (RER) had frequently occurred in DMH-induced tumors. In contrast, no such instability were detected in spontaneous tumors in Min mice.
All these data indicate that genes involved in colon tumorgenesis may be somewhat different between spontaneous tumors and induced tumors, and also between human FAP (familial adenomatous poliposis) and its mouse model.
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Research Products
(6 results)
