Overcoming the activity of mammary carcinoma suppressor gene in Copenhagen rats by v-H-ras oncogene transfer into mammary epithelial cells in situ.

Susceptibility to mammary cancer in rats is genetically controlled by both susceptibility and suppressor genes. The Copenhagen (COP) rat strain is highly resistant to both spontaneous and induced mammary carcinogenesis. The resistant trait is due to the inheritance of an autosomal dominant allele termed mammary carcinoma suppressor (mcs) gene. To test whether the activity of mcs gene can suppress the transforming potential of an activated oncogene, we introduced v-H-ras oncogene into COP mammary epithelial cells in situ using a replication-defective retroviral vector. v-H-ras transfer caused the rapid development of mammary carcinomas at high multiplicities. Hormonal promotion further increased the penetrance of the activated ras gene. Compared with the mammary carcinoma-susceptible Wistar Furth (WF) rat strain, tumor development in the COP rat followed analogous kinetics. However, COP tumors were more differentiated and less locally invasive than were WF tumors. The possible role of the mcs gene in mammary differentiation is discussed.