Figure 2

Postulated roles for TGF-β and HGF/SF during the life cycle of the mammary gland. TGF-βs have complex roles during mammary development, according to their concentration. Although most of the experimental evidence points to inhibition of ductal branching, preliminary analysis of both TGF-β₁- and SMAD-3-null mutant mice suggest a requirement for TGF-β₁ for mammary development. Thus, TGF-βs have both concentration- and context-dependent effects on mammary gland development. HGF/SF promotes ductal outgrowth through an integrin-mediated process. This action is inhibited by TGF-β₁, indicating that interactions between these growth factors play a role in ductal spacing as the mammary gland grows out over the fat pad. During pregnancy, TGF-βs appear to inhibit alveolar development and suppress milk formation. The decline in TGF-β expression at the end of pregnancy appears to be necessary for full lobuloalveolar development and lactation. After weaning involution is begun, with TGF-β₃ inducing apoptosis in the lobuloalveolar structures through an autocrine mechanism.