EXPRESSION OF THE PROTOONCOGENE JUN IS INDUCED IN THE RAT PANCREAS BYCERULEIN INFUSION

Cholecystokinin (CCK) can stimulate secretion and DNA synthesis in pan creatic acinar cells. Hyperstimulation with cerulein (a CCK analogue) induces acute edematous pancreatitis. To study the effects of in vivo pancreatic stimulation with cerulein, we analyzed the expression of th e protooncogenes jun, myc, and fos on the mRNA and protein levels. RNA and protein were extracted from the pancreas of rats administered an infusion of cerulein, 10 mu g/kg/h (Group A) or 0.25 mu g/kg/h (Group B), or saline (Group C) and sacrificed 2, 4, and 6 h after beginning t he infusion and 0, 12, and 24 h and 2, 4, and 6 days after completing the infusion period. Transcript levels were studied using slot-blot an alysis. protein expression was studied using Western blot and immunohi stochemistry. No changes were found for the expression of protooncogen es myc and fos on either the transcript or the protein levels. Higher jun mRNA levels were found in Group A than in Group B or C, particular ly after 2 h of infusion and 12, 24, and 48 h after the end of a 12-h cerulein infusion, No significant difference was observed in Groups B and C. The jun protein behavior was similar in Groups A and B, reveali ng two peaks: one early during infusion and a second one after the end of a 12-h cerulein infusion. Jun protein was found mainly in the acin ar cells. In conclusion, (1) acinar cells in the rat pancreas respond to cerulein stimulation by increasing the expression of jun; (2) in vi vo high doses of cerulein increase the jun mRNA and jun protein levels , whereas low doses raise only the protein levels; and (3) myc and fos are apparently uninfluenced by cerulein administration.