DIRECT TRANSFORMING ACTIVITY OF TGF-BETA ON RAT FIBROBLASTS

Treatment of NRK 536 fibroblasts with EGF and transforming growth fact or type beta (TGF-beta) is known to lead to the reversible induction o f the transformed phenotype in a large percentage of cells. Maintenanc e of the transformed state is dependent on the continuous presence of the cytokines. Here we show that treatment of these cells with TGF-bet a alone leads to the formation of a small percentage of colonies, the majority of which stably retain the transformed phenotype after remova l of the cytokine. Colony induction is dependent on the concentration of TGF-beta originally present. Stably transformed cells grow in soft agar without further addition of exogenous TGF-beta, and exhibit criss -cross morphology in monolayer culture and a diffuse actin pattern. Tr ansformation of NRK 536 cells can be demonstrated only for individuali zed cells treated with TGF-beta in soft agar, as treatment in monolaye r leads to the induction of apoptosis in newly transformed cells by ne ighboring normal cells. Transformation of NRK 536 fibroblasts by TGF-b eta is not due to the induction of point mutations by TGF-beta. (C) 19 95 Wiley-Liss, Inc.