IGF and insulin action in the mammary gland: lessons from transgenic and knockout models

Transgenic and knockout mice have become valuable experimental systems with which to study specific molecular events within the mammary gland of an intact animal. These models have provided a wealth of information about the effects of a number of oncogenes and growth factors. This review focuses on results obtained from the application of transgenic and knockout models to determine the roles of insulin and insulin-like growth factors (IGF) in the regulation of mammary gland development, lactation and tumorigenesis. Transgenic models which overexpress IGF-I or -II display specific alterations in mammary gland development and an increased incidence of mammary tumors. Analysis of mammary gland development in knockout mice which are deficient in IGF-I or the IGF-I receptor supports the conclusion that the IGF system is important for normal mammary gland development. This review discusses these observations in detail and attempts to fit them into a larger picture of IGF and insulin action in the mammary gland.