TGF-BETA(1) INDUCES MORPHOGENESIS OF BRANCHING CORDS BY CLONED MAMMARY EPITHELIAL-CELLS AT SUBPICOMOLAR CONCENTRATIONS

The factors which control the formation of lactiferous ducts during ma mmary gland development are not yet fully understood. To address this issue, we assessed the effect of the multifunctional cytokine transfor ming growth factor-beta-1 (TGF-beta(1)) on the morphogenetic propertie s of TAC-2.1 mammary epithelial cells grown in collagen gels. Here we demonstrate that TGF-beta(1) has a biphasic effect on these cells: whe reas relatively high concentrations (0.5-5 ng/ml) inhibit colony forma tion, lower concentrations (5-100 pg/ml = 200fM-4pM) stimulate colony elongation and branching, resulting in the formation of an extensive n etwork of epithelial cords. We suggest that in concert with other regu latory factors; low concentrations of TGF-beta(1) promote mammary glan d ductal morphogenesis. (C) 1996 Academic Press, Inc.