Expression of the IGFs, IGF-IR and IGFBPs in the normal mammary gland and breast

The insulin-like growth factors (IGFs) and the IGF type I receptor (IGF-IR) have demonstrated functions in normal mammary epithelial growth in mice and have been implicated in breast cancers in humans. Recent data support the hypothesis that the two IGF ligands, IGF-I and IGF-II, are differentially regulated and have different functions in developing mammary tissue. Emerging data suggest the possibility that differential actions of IGF-I and IGF-II may be mediated, in part, through binding to alternate forms of the insulin and IGF receptors. A major unresolved issue in both normal development and abnormal growth of mammary/breast tissue is the extent to which circulating or locally expressed IGFs mediate growth. Moreover, the family of IGF binding proteins (IGFBPs), which function both to modulate IGF actions and as IGF-independent mediators of growth, also are present in the circulation and synthesized locally in normal mammary tissue. Here, we review data on local expression of the IGFs, IGF receptors and IGFBPs and discuss the possible roles for these molecules in normal growth of mammary and breast tissue.