title: Antiproliferative effects of interferon alpha on human pancreatic carcinoma cell lines are associated with differential regulation of protein kinase C isoenzymes.
abstract: BACKGROUND
  The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Medizinische Klinik and Poliklinik, Khnikum Benjamin Franklin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rosewicz
authors.forename: M
authors.initials: M
authors.lastname: Weder
authors.forename: A
authors.initials: A
authors.lastname: Kaiser
authors.forename: E O
authors.initials: EO
authors.lastname: Riecken
mesh_terms: D015153:Blotting, Western; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology*; D002455:Cell Division; D004586:Electrophoresis; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
chemical_list: D016898:Interferon-alpha; D007527:Isoenzymes; D011493:Protein Kinase C