Site of expression and biological function of the rat mammary carcinoma suppressor gene

Abstract

The rat mammary carcinoma suppressor (MCS) gene is an autosomal dominant gene found in the Copenhagen (Cop) rat that specifically prevents carcinogen-induced and spontaneous mammary carcinomas. Mammary cells from the Wistar-Furth (WF) rat, which do not carry the MCS gene, were grafted into ectopic sites in WF X Cop and WF X Fischer 344 hybrid rats. Only the former hybrid carried the MCS gene. These chimeric rats were then treated with 7,12-dimethylbenz[a]anthracene (DMBA) and the development of mammary carcinomas was followed. The results suggested that the main site of MCS activity was within the mammary parenchyma. However, a minor abscopal effect of this gene was also observed. Ectopic mixed mammary glands composed of a mixture of Cop and WF cells were also examined for susceptibility to DMBA-induced carcinogenesis. The presence of Cop cells did not inhibit tumor development from WF cells in these mixed glands. Finally, graft sites in which palpable tumors did not develop were examined for focal epithelial lesions. The MCS gene was found to inhibit completely the formation of microcarcinomas, but did not affect the development of alveolar hyperplasias.