Related Experiment Videos
Interleukin-10-deficient mice and inflammatory bowel disease associated cancer development
S Sturlan1, G Oberhuber, B G Beinhauer
1Department of General Surgery, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Abstract:
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 beta type II receptor. Microsatellite instability was analysed at eight chromosomal loci and plasma levels of transforming growth factor beta1 (TGF-beta1) 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-beta1 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-beta1 plasma levels correspond to the high incidence of dysplasia and cancer. Normal expression of the TGF-beta II receptors hints at genetic alterations in other members of the TGF-beta receptor signal transduction pathway.
Insights
Interleukin-10 (IL-10) deficient mice develop colorectal cancer. This study found no mutations in key cancer genes, suggesting other pathways, like elevated TGF-beta1, are involved in tumor development.
Area of Science:
- Gastroenterology
- Oncology
- Immunology
Background:
- Interleukin-10 (IL-10) deficiency in mice models human inflammatory bowel disease-associated colorectal cancer.
- Understanding the genetic basis of tumorigenesis in IL-10 deficient mice is crucial for human cancer research.
Purpose of the Study:
- To identify mutations in oncogenes and tumor suppressor genes contributing to colorectal cancer in IL-10 deficient mice.
- To investigate the role of specific genes and transforming growth factor beta1 (TGF-beta1) in tumor development.
Main Methods:
- Screening for mutations in K-ras and p53 genes using single-strand-conformation polymorphism.
- Immunohistochemical analysis of P53, APC, MSH2, and TGF-beta receptor type II.
- Microsatellite instability analysis and plasma TGF-beta1 level measurement.
Main Results:
- Colorectal cancer incidence reached 65% in IL-10 deficient mice by 10-31 weeks.
- No mutations were detected in the screened K-ras, p53, APC, or Msh2 genes.
- Significantly elevated plasma TGF-beta1 levels were observed in IL-10 deficient mice compared to wild-type controls.
Conclusions:
- The development of colorectal cancer in IL-10 deficient mice likely involves genetic alterations beyond the commonly screened oncogenes and tumor suppressor genes.
- Elevated TGF-beta1 levels correlate with increased cancer incidence, suggesting its involvement in the tumorigenesis pathway.
- Further investigation into the TGF-beta signaling pathway is warranted to understand the mechanisms driving cancer in this model.