Effects of transforming growth factor beta on growth of human mammary epithelial cells in culture

Normal human mammary epithelial cells (HMEC) from different individual reduction mammoplasty specimens were all growth inhibited, and showed a flattened, elongated morphology in response to human recombinant transforming growth factor beta 1 (TGF beta). The degree of growth inhibition varied among specimens, but none of the normal HMEC maintained growth in the continued presence of TGF beta. The degree of growth inhibition also varied with cell age in vitro, cells closer to senescence being more sensitive. TGF beta sensitivity was additionally assayed in two established cell lines derived from one of the reduction mammoplasty specimens after exposure to benzo(a)pyrene. Although varying degrees of growth inhibition and morphologic changes were observed in the cell lines, both lines contained populations that maintained active growth in the presence of TGF beta. Subclones of these lines demonstrated a great plasticity in their growth response to TGF beta, with individual clones ranging from strongly growth inhibited to nearly unaffected. These results suggest that multiple factors influence the extent of TGF beta-induced growth effects on both normal and transformed mammary epithelial cells, and that some of these factors may act through epigenetic mechanisms.