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 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.
Rosewicz
S
S
Department of Gastroenterology, Medizinische Klinik and Poliklinik, Khnikum Benjamin Franklin, Berlin, Germany.
Weder
M
M
Kaiser
A
A
Riecken
E O
EO
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
D016898:Interferon-alpha; D007527:Isoenzymes; D011493:Protein Kinase C