The Insulin-Like Growth Factor System in Normal Mammary Gland Function

Abstract

Insulin-like growth factors (IGF) are now known to play an important role in normal mammary gland development and have been implicated as risk factors in the etiology of breast cancer. Studies in genetically engineered mouse models have demonstrated that the IGF system acts within the mammary epithelium at key developmental stages to either stimulate cell cycle progression or inhibit cell death. The importance of these two actions to mammary gland development varies with the different developmental stage. Cell cycle effects appear to predominate during virgin ductal development and early pregnancy while cell survival effects are important for initiation and maintenance of lactation. This variation with stage of development most likely reflects changes in specific populations of epithelial cells within the gland. Relatively little information exists however on the actions of the IGF system during fetal or very early postnatal development. In addition much remains to be learned about the intracellular signaling mechanism that mediate the effects of IGFs on the different populations of epithelial cells present within the gland. This review summarizes the current state of knowledge concerning IGF actions, and mechanisms of action, within the normal mammary gland.