Gene expression changes associated with chemically induced rat mammary carcinogenesis.

Experimentally induced models of breast carcinogenesis in the rat are widely used for studying the biology of breast cancer and for developing and evaluating cancer prevention and control strategies. However, very little is known about gene expression changes that are associated with experimentally induced mammary carcinogenesis. This paper reports the identification, by differential display of mRNA and molecular cloning, of seven cDNA fragments of gene transcripts overexpressed in mammary carcinomas induced by 1-methyl-1-nitrosourea. These genes included the rat homologues of human galectin-7 gene, the human/mouse melanoma inhibitory activity/bovine chondrocyte-derived retinoic acid sensitive protein gene, the mouse stearoyl-CoA desaturase-2 gene, and the mouse endo B cytokeratin/human cytokeratin-18 gene. Although each of these genes has been implicated in some aspect of carcinogenesis in other organs, this paper is the first report of their overexpression in chemically induced mammary carcinomas. Two previously uncharacterized gene transcripts were also identified. A comparison of the expression levels of several genes in mammary carcinomas with those in the normal mammary gland tissue of virgin rats, mid-stage pregnant rats, and of day 1 postpartum lactating dams indicated that the overexpression of several genes observed in mammary carcinomas could not be accounted for by either a difference in the mammary epithelial content between mammary carcinoma and normal mammary tissue or by mammary epithelium-specific proliferation associated with pregnancy. Several genes were also overexpressed in rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene but not in azoxymethane-induced rat colon adenocarcinomas. The genes identified in this study may therefore represent mammary carcinoma-specific molecular markers that may be helpful in investigations of mammary carcinogenesis and its prevention.