Genetically engineered rodent models of mammary gland carcinogenesis: An overview

Breast cancer is a multifactorial disease that develops as a result of inte ractions among genetic. environmental, and hormonal factors. Multiple genet ic derangements are believed to be involved in the pathogenesis of breast c ancer, including the inactivation of tumor suppressor genes and/or the disr egulation of proto-oncogenes. Age, hormones, and environmental factors furt her influence these genetic derangements. Spontaneous and chemically induce d animal models of breast cancer have been limited in their usefulness. The advent of targeted gene mutations has allowed for a more specific explorat ion of the pathogenesis of breast cancer by creating mouse models that mimi c single or multiple gene alterations found in human mammary tumors. The ge nes targeted in these models include mouse mammary tumor integration sites and genes that encode for growth regulators, signal transduction proteins, cell cycle proteins, and cell matrix proteinases. In this review. I summari ze tumor morphology and the relevance of each model to the pathogenesis and progression of human breast cancer. These models have great potential for elucidating the multistep process of mammary gland carcinogenesis and for c ontributing to the identification of novel therapeutic targets.