Carcinogenesis, Vol. 22, No. 4, 665-671,
April 2001
© 2001 Oxford University Press
CARCINOGENESIS |
Interleukin-10-deficient mice and inflammatory bowel disease associated cancer development
Department of General Surgery and
1 Department of Clinical Pathology, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria and
2 Institute for Surgical Research, The National Hospital, University of Oslo, Oslo, Norway
Interleukin-10-deficient mice develop colitis and colorectal cancer similar to the inflammatory bowel disease associated cancer in humans. The aim of this study was to identify possible mutations of oncogenes and tumour suppressor genes involved in tumorigenesis in Interleukin-10 (IL-10)-deficient mice. Twenty colon carcinomas from IL-10-deficient mice were screened for mutations in the K-ras and p53 genes by `cold' single-strand-conformation polymorphism. Immunohistochemical staining was performed to detect mutations in the proteins P53, APC and MSH2, and the transforming growth factor ß type II receptor. Microsatellite instability was analysed at eight chromosomal loci and plasma levels of transforming growth factor ß1 (TGF-ß1) were also measured. At 9 weeks, 14% of the animals developed colorectal cancer, and at 10–31 weeks the incidence of carcinoma was 65%. No mutations were detected in the analysed oncogene and tumour suppressor genes. Plasma TGF-ß1 levels in IL-10-deficient mice 10–31 weeks old were higher than in wild-type littermates e.g. 45.7 ± 4.6 ng/ml versus 19.8 ± 4.5 ng/ml (P < 0.01). No alterations in K-ras, p53, Apc and Msh2 genes suggests that other genes are involved in the development of these tumours. Elevated TGF-ß1 plasma levels correspond to the high incidence of dysplasia and cancer. Normal expression of the TGF-ß II receptors hints at genetic alterations in other members of the TGF-ß receptor signal transduction pathway.
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