TGF-beta1 induces morphogenesis of branching cords by cloned mammary epithelial cells at subpicomolar concentrations.

The factors which control the formation of lactiferous ducts during mammary gland development are not yet fully understood. To address this issue, we assessed the effect of the multifunctional cytokine transforming growth factor-beta-1 (TGF-beta1) on the morphogenetic properties of TAC-2.1 mammary epithelial cells grown in collagen gels. Here we demonstrate that TGF-beta1, has a biphasic effect on these cells: whereas relatively high concentrations (0.5-5 ng/ml) inhibit colony formation, lower concentrations (5-100 pg/ml = 200fM-4pM) stimulate colony elongation and branching, resulting in the formation of an extensive network of epithelial cords. We suggest that, in concert with other regulatory factors, low concentrations of TGF-beta1 promote mammary gland ductal morphogenesis.