GENETIC-REGULATION OF MAMMARY CARCINOGENESIS IN THE RAT BY SUSCEPTIBILITY AND SUPPRESSOR GENES

Rat strains differ in their susceptibilities to mammary carcinogenesis. Strains such as Wistar-Furth are very susceptible to chemically induced carcinogenesis. This phenotype is controlled by autosomally dominant susceptibility genes. Strains such as the Copenhagen are resistant to spontaneous and induced mammary carcinogenesis. This phenotype is controlled by an autosomal dominant gene termed the mammary carcinoma suppressor (MCS). Strains with intermediate susceptibility such as the F344 carry neither the MCS nor susceptibility genes. Both the MCS and susceptibility genes are chiefly active within the mammary parenchyma. Both genes act at carcinogenesis stages beyond carcinogen metabolism and DNA adduction. The MCS gene completely inhibits both palpable and microcarcinomas. It does not inhibit focal alveolar hyperplasias. Its gene product acts solely within the mammary epithelial cell in which it is produced. We are currently investigating the interactions of various oncogenes and the MCS gene. In addition, efforts are underway to identify and clone this gene.