AbstractPancreatic cancer is an extremely aggressive malignancy. The factors allowing human pancreatic cancer cells to escape normal growth constraints are not known. However, it has been proposed that certain cancer cells may obtain a growth advantage as the result of a lack of responsiveness to negative growth regulators such as transforming growth factor-beta 1 (TGF-β1). We now show that two established pancreatic carcinoma cell lines, COLO 357 and PANC-I, are sensitive to growth inhibition by TGF-β1. The growth of COLO 357 cells is inhibited by 50% when incubated in the presence of TGF-β1 (5 ng/ml) under low serum conditions (0.5%). PANC-I cells are growth inhibited by 25% under the same conditions. In COLO 357 cells, but not PANC-I cells, TGF-β1 also causes a marked alteration in cell morphology. In both cell lines, TGF-β1 induces TGF-β1 mRNA levels in a time and dose-dependent manner. However, TGFβ1 does not increase the amount of TGF-β2 or TGF-β3 mRNA in these cells. In spite of its growth inhibitory effects, TGF-β1 fails to suppressc-mycmRNA levels. These findings suggest that TGF-β1 inhibits the growth of human pancreatic cancer cells and point to a significant dysfunction in the ability of TGF-β1 to suppressc-mycexpression in these cells.