ESCAPE FROM THE ANTIPROLIFERATIVE EFFECT OF TRANSFORMING GROWTH FACTOR-BETA(1) IN LLC-PK1 RENAL EPITHELIAL-CELLS

Transforming growth factor-beta(1) (TGF-beta(1)) usually inhibits prol iferation of epithelial cells. We find that LLC-PK1 renal tubular epit helial cells develop rapid in vitro resistance to the inhibitory effec ts of TGF-beta(1) and subsequently proliferate in response to TGF-beta (1). This unique response to TGF-beta(1) is not observed in another re nal tubular epithelial cell line (MDCK cells). The proliferative respo nse to TGF-beta(1) is additive to that produced by other growth factor s. The proliferative response to TGF-beta(1) occurs despite an effect of TGF-beta(1) to suppress epidermal growth factor stimulated c-myc mR NA as determined by Northern analyses. These results suggest that LLC- PK1 cells develop rapid resistance to TGF-beta(1) inhibition of prolif eration in vitro and that this resistance occurs despite continued sup pression of c-myc mRNA.