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. 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.

journal_name

Gut

journal_title

Gut

authors

Rosewicz S,Weder M,Kaiser A,Riecken EO

doi

10.1136/gut.39.2.255

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

255-61

issue

2

eissn

0017-5749

issn

1468-3288

journal_volume

39

pub_type

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