TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA-1) INHIBITS PANCREATIC ACINAR CELL-GROWTH

Effects of transforming growth factor (TGF)-beta-1 on mouse pancreatic acinar cell growth and rapid intracellular responses to cholecystokinin (CCK) were examined in vitro. TGF-beta-1 inhibited [H-3]thymidine incorporation stimulated by either the CCK analogue caerulein, epidermal growth factor, or insulin. TGF-beta-1 inhibition of growth stimulated by a maximal dose of caerulein (1 nM) was dose dependent with one-half maximal effects occuring at approximately 5 pM and maximal inhibition seen with 30 pM. In contrast to its effects on CCK-stimulated [H-3]thymidine incorporation, TGF-beta-1 had no effect on CCK-stimulated increases in amylase release or intracellular Ca2+ concentration. To determine whether TGF-beta-1 might be an autocrine growth regulator, pancreatic mRNA was probed for the presence of TGF-beta-1 transcripts. TGF-beta-1 mRNA was not detected in whole pancreas but was detectable with increasing abundance over time in primary cultures of pancreatic acinar cells. The appearance of the TGF-beta-1 mRNA corresponded to the period of rapid cellular proliferation in vitro. These results suggest that TGF-beta-1 may be an autocrine growth inhibitor in the pancreas and that the inhibitory effects of TGF-beta-1 on pancreatic acinar cell growth occur at sites distal to those involved in stimulus-secretion coupling.