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 developi ng and evaluating cancer prevention and control strategies. However, v ery 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 clo ning, of seven cDNA fragments of gene transcripts overexpressed in mam mary carcinomas induced by 1-methyl-1-nitrosourea. These genes include d the rat homologues of human galectin-7 gene, the human/mouse melanom a inhibitory activity/bovine chondrocyte-derived retinoic acid sensiti ve protein gene, the mouse stearoyl-CoA desaturase-2 gene, and the mou se endo B cytokeratin/human cytokeratin-18 gene. Although each of thes e genes has been implicated in some aspect of carcinogenesis in other organs, this paper is the first report of their overexpression in chem ically induced mammary carcinomas. Two previously uncharacterized gene transcripts were also identified. A comparison of the expression leve ls of several genes in mammary carcinomas with those in the normal mam mary gland tissue of virgin rats, mid-stage pregnant rats, and of day 1 postpartum lactating dams indicated that the overexpression of sever al 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 overe xpressed in rat mammary carcinomas induced by 7,12-dimethylbenz[a]anth racene but not in azoxymethane-induced rat colon adenocarcinomas. The genes identified in this study may therefore represent mammary carcino ma-specific molecular markers that may be helpful in investigations of mammary carcinogenesis and its prevention. (C) 1997 Wiley-Liss, Inc.