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We have used transgenic mice that carry an activated c-neu oncogene driven by a mouse
mammary tumor virus (MMTV) promoter to assess the stepwise progression of carcinogenesis
in mammary epithelium. Unlike the stochastic occurrence of solitary mammary tumors
in transgenic mice bearing the MMTV/c-myc or the MMTV/v-Ha-ras oncogenes, transgenic
mice uniformly expressing the MMTV/c-neu gene develop mammary adenocarcinomas that
involve the entire epithelium in each gland. Because these tumors arise synchronously
and are polyclonal in origin, expression of the activated c-neu oncogene appears to
be sufficient to induce malignant transformation in this tissue in a single step.
In contrast, expression of the c-neu transgene in the parotid gland or epididymis
leads to benign, bilateral epithelial hypertrophy and hyperplasia which does not progress
to full malignant transformation during the observation period. These results indicate
that the combination of activated oncogene and tissue context are major determinants
of malignant progression and that expression of the activated form of c-neu in the
mammary epithelium has particularly deleterious consequences.