The Preneoplastic Phenotype in Murine Mammary Tumorigenesis

Preneoplastic lesions in murine mammary tumorigenesis have been extensively investigated over the past 50 years. The two general types of lesion that have malignant potential are the alveolar hyperplasias represented by the classical hyperplastic alveolar nodule and the ductal hyperplasias. The former type of lesion is induced by viral, chemical and hormonal agents; the latter by chemical agents and specific genetic alterations. Individual animal models have been utilized to elucidate the basic biological properties of the lesions and some of the basic molecular alterations. The biological phenotype of the two types of lesions include immortalization and epithelial hyperplasia. The ductal hyperplasias are distinguished from the alveolar hyperplasias by their pattern of epithelial hyperplasia and their extent of aneuploidy. The molecular alterations underlying epithelial hyperplasia are numerous and dependent on the particular animal model. An important issue for future studies is how faithfully any of these models mimic human premalignant progression. A minimal set of criteria is proposed that includes morphological progression, hormone dependence and genetic instability. It is likely that hyperplasias from a specific mouse model will represent a subset of the lesions found in human disease. Analogous hyperplasias from several defined genetic models, adequately characterized at the biological and molecular levels, would provide appropriate models for testing chemopreventive agents.