A mouse model of oral-esophageal carcinogenesis

Squamous cancers of the oral cavity and esophagus are common worldwide. A number of environmental factors as well as genetic alterations have been identified. However, the specific combination of genetic events and their interplay with environmental carcinogens are largely unknown. Furthermore, no good animal model existed to study the molecular changes important in the induction and progression of the disease. Here we summarize the efforts made to establish a mouse model of oralesophageal carcinogenesis. Cyclin D1 overexpressing (L2D1+) mice were generated using an EBV promoter to specifically target the oral cavity and the esophageal squamous epithelium. Besides analyzing different environmental factors, such as nitrosamines and zinc deficiency, cyclin D1 transgenic mice were crossbred with p53-deficient mice. While L2D1+ mice exhibited a phenotype of dysplasia, different combinations of mice resulted in invasive oral-esophageal cancer. This mouse model provides a well-defined and reproducible model of oralesophageal cancer that should be useful for testing chemopreventive, diagnostic, and therapeutic strategies.