ANTIPROLIFERATIVE EFFECTS OF INTERFERON-ALPHA ON HUMAN PANCREATIC-CARCINOMA CELL-LINES ARE ASSOCIATED WITH DIFFERENTIAL REGULATION OF PROTEIN-KINASE-C ISOENZYMES

Background-The molecular mechanisms mediating the antiproliferative ef fects of interferon alpha on human pancreatic carcinoma cells are poor ly understood. Aim-To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive an d resistant human pancreatic tumour cell lines. Methods-The ductal hum an pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigat ed. Anchorage dependent and independent growth was determined by cell number and a human tumour clonogenic assay. Interferon alpha receptor expression was examined by reverse-transcriptase polymerase chain reac tion and electrophoretic mobility shift assay. Protein kinase C isoenz yme expression was evaluated by western blotting using monospecific po lyclonal antibodies. Results-Interferon alpha treatment results in a t ime and dose dependent inhibition of anchorage dependent and independe nt growth in Capan 1 cells while Capan 2 cells were not affected by in terferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells w as paralleled by a profound decrease of protein kinase C alpha and zet a expression while these isoenzymes were unaffected in the interferon resistant cell line Capan 2. Conclusion-Inhibition of protein kinase C isoenzyme expression might determine the sensitivity of a given pancr eatic carcinoma to respond to the antiproliferative action of interfer on alpha.