Animal models for breast cancer.

Rodent mammary tumors induced by chemical carcinogens have proven to be very useful in the genetic analysis of initiation, promotion and progression of mammary carcinogenesis. We are studying rat mammary carcinomas induced by the chemical carcinogen, N-nitroso-N-methylurea. The earliest genetic event observed in the mammary gland is the activation of Ha-ras oncogenes, which is followed by promotion of the initiated cells by hormones involved in puberty. Preferential amplification of the mutated Ha-ras allele, of PRAD-1 and IGF2, loss of expression of the mitogenic growth factor gene, MK, and mutation in the tumor suppressor gene, p53, are seen in the mammary tumors during tumor progression.