Background: The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood.
Aim: To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines.
Methods: The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. 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 reaction and electrophoretic mobility shift assay. Protein kinase C isoenzyme expression was evaluated by western blotting using monospecific polyclonal antibodies.
Results: Interferon alpha treatment results in a time and dose dependent inhibition of anchorage dependent and independent growth in Capan 1 cells while Capan 2 cells were not affected by interferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells was paralleled by a profound decrease of protein kinase C alpha and zeta 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 pancreatic carcinoma to respond to the antiproliferative action of interferon alpha.