Type beta transforming growth factor: a bifunctional regulator of cellular growth.

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Abstract
Type .beta. transforming growth factor (TGF-.beta.) is a 2-chain polypeptide of 25,000 daltons isolated from many tissues, including bovine kidney, human placenta and human platelets. It is characterized by its ability to stimulate reversible transformation of nonneoplastic murine fibroblasts, as measured by the formation of colonies of these cells in soft agar (ED50 = 4 pM TGF-.beta. for NRK fibroblasts). The response of cells to TGF-.beta. is bifunctional, in that TGF-.beta. inhibits the anchorage-dependent growth of NRK fibroblasts and of human tumor cells by increasing cell cycle time. The anchorage-independent growth of many human melanoma, lung carcinoma and breast carcinoma cell lines is inhibited by TGF-.beta. at concentrations in the same range as those that stimulate colony formation of NRK fibroblasts (average ED50 = 10-30 pM TGF-.beta. for inhibition). Whereas epidermal growth factor and TGF-.beta. synergize to induce anchorage-independent growth of NRK fibroblasts, their effects on the growth of A-549 human lung carcinoma cells are antagonistic. The bifunctional response of cells to TGF-.beta. is further demonstrated in Fischer rat 3T3 fibroblasts transfected with a cellular myc gene. In these cells TGF-.beta. synergizes with platelet-derived growth factor to stimulate colony formation but inhibits the colony formation induced by epidermal growth factor. The effects of TGF-.beta. on cells are not a function of the peptide itself, but rather of the total set of growth factors and their receptors that is operant in the cell at a given time.