Biological and molecular characteristics of the premalignant mouse mammary gland

Preneoplastic lesions in murine mammary tumorigenesis have been extensively investigated over the past 50 years. The two general types of lesions that have malignant potential are the alveolar hyperplasias represented by the classical hyperplastic alveolar nodule (HAN) and the ductal hyperplasias (DHs) represented by usual DH and ductal carcinoma in situ (DCIS). 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 DHs are distinguished from the alveolar hyperplasias by their pattern of epithelial hyperplasia, extent of ovarian hormone dependence, activation of telomerase and presence of aneuploidy. The molecular alterations underlying mammary epithelial hyperplasia are numerous and dependent on the particular animal model. An important issue 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. Analogous hyperplasias from several defined genetic models, adequately characterized at the biological and molecular levels, would provide appropriate models for testing chemopreventive agents and for elucidating secondary molecular events causative for malignant behavior.