Cyclin D1expression during rat mammary tumor development and its potential role in the resistance of the Copenhagen rat

Abstract Background Resistance to mammary tumorigenesis in Copenhagen rats isassociated with loss of early preneoplastic lesions known as intraductalproliferations. The cause of this disappearance, however, is unknown. Results There were no differences in the numbers of lesions in mammarywhole-mounts prepared from Copenhagen or Wistar-Furth rats at 20 or 30 daysafter N-methyl-N-nitrosourea treatment, but at 37 days therewere significantly fewer lesions in Copenhagen glands. Furthermore, lesions inCopenhagen glands were exclusively intraductal proliferations, whereas inWistar-Furth glands more advanced lesions were also present.Immunohistochemical staining showed frequent cyclin D1 overexpression inWistar-Furth lesions at 37 days, but not in Copenhagen lesions. There were,however, no differences in p16 INK4a protein expression,bromodeoxyuridine labeling and apoptotic indices, or mast cell infiltrationbetween Copenhagen and Wistar-Furth lesions at any time. Conclusions Overexpression of cyclin D1 in preneoplastic lesionsmay be important in the development of mammary tumors in susceptible rats,although this overexpression does not appear to cause significant changes incell kinetics. Furthermore, the low levels of cyclin D1 expressionin Copenhagen intraductal proliferations may play a role in the resistance ofthese rats to mammary tumorigenesis