In wap-ras transgenic mice, tumor phenotype but not cyclophosphamide-sensitivity is affected by genetic background.

Male wap-ras transgenic mice develop adenocarcinomas in salivary and/or mammary tissue by age 1 year. When the wap-ras transgene was bred into the FVB/N strain, males developed multiple mammary tumors between 1.5 and 3 mo. of age, but no salivary tumors. Crosses between ras/FVB mice and other strains produced moderate changes in mammary tumor onset and severity, but no salivary tumors. Histopathological analysis of 62 adenocarcinomas from 18 mice yielded: 14 tumors with areas of squamous metaplasia, many tumors with epithelium-lined cysts, few immune cells in tumors, and no lung metastases. Cyclophosphamide delayed tumor onset and inhibited the growth of established tumors. Our results suggest that wap-ras mice will be useful for studying ras-mediated tumor genetics and should be a good assay system for both preventative and curative anticancer therapies.