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.