Somatic mutational mechanisms involved in intestinal tumor formation in Min mice

We have demonstrated previously that intestinal tumor formation in B6 Min/+ mice is always accompanied by loss of the wild-type adenomatous polyoposis coli (Apc) allele and that intestinal tumor multiplicity in B6 Min/+ mice can be significantly increased by treatment with a single dose of N-ethyl-N...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-05, Vol.57 (10), p.1999-2006
Main Authors: SHOEMAKER, A. R, LUONGO, C, MOSER, A. R, MARTON, L. J, DOVE, W. F
Format: Article
Language:English
Subjects:
Alleles
Animal tumors. Experimental tumors
Animals
Biological and medical sciences
Carcinogens
Ethylnitrosourea
Experimental digestive system and abdominal tumors
Female
Gene Deletion
Gene Expression Regulation, Neoplastic
Genes, APC
Genes, ras
Intestinal Neoplasms - chemically induced
Intestinal Neoplasms - genetics
Male
Medical sciences
Mice
Mice, Inbred Strains
Mutation
Tumors
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Summary:We have demonstrated previously that intestinal tumor formation in B6 Min/+ mice is always accompanied by loss of the wild-type adenomatous polyoposis coli (Apc) allele and that intestinal tumor multiplicity in B6 Min/+ mice can be significantly increased by treatment with a single dose of N-ethyl-N-nitrosourea (ENU). Here, we show that some tumors from ENU-treated Min/+ mice can form without complete elimination of Apc+. At least 25% of these tumors acquired somatic Apc truncation mutations. Interestingly, some ENU-induced tumors demonstrated loss of the Apc+ allelic marker examined by the quantitative PCR assay used here. Using two methods of mutation detection, we identified no Apc mutations in at least 12% of the tumors from ENU-treated B6 Min/+ mice. Finally, no H- or K-ras-activating mutations were detected in intestinal tumors from either untreated or ENU-treated Min/+ mice. The majority of somatic human APC mutations in intestinal tumors lead to APC truncation. Our results demonstrate that somatic Apc truncation mutations also frequently occur in ENU-induced intestinal tumors in Min mice.
ISSN:0008-5472
1538-7445