TGF-BETA INDUCTION OF EXTRACELLULAR-MATRIX ASSOCIATED PROTEINS IN NORMAL AND TRANSFORMED HUMAN MAMMARY EPITHELIAL-CELLS IN CULTURE IS INDEPENDENT OF GROWTH EFFECTS

We have previously characterized a human mammary epithelial cell (HMEC) culture system for the effects of TGFbeta1 on cell growth. In the current report, the effects of TGFbeta1 on synthesis and secretion of proteins associated with the extracellular matrix and proteolysis were examined. In particular, we compared the TGFbeta responses of normal finite lifespan HMEC, which are growth inhibited by TGFbeta, to two immortally transformed cell lines derived from the normal HMEC. One of these lines maintains active growth in the presence of TGFbeta and the other shows partial growth inhibition. In contrast to the differing effects of TGFbeta on cell growth, we found that all these cell types showed strong induction of most of the mRNA and protein species examined, including fibronectin, collagen IV, laminin, type IV collagenase, urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor 1 (PAI-1). The profile of TGFbeta1 binding proteins was the same in HMEC that were, and were not growth suppressed by TFGbeta. Therefore, the effects of TGFbeta on cell growth could be dissociated from its effects on specialized responses, indicating that within this one cell type there must be at least two independent pathways for TGFbeta activity, one which leads to cessation of proliferation and one which induces a specific set of cellular responses. This cell system may be useful for examining the pathway of TGFbeta induced growth inhibition using closely matched cells which vary in their growth-induced response but retain similar specialized responses to TGFbeta.