Increased expression of NF-κB subunits in human pancreatic cancer cells

Background. Activation of NF-kappaB-dependent antiapoptotic genes may factor in the chemoresistance of pancreatic cancer. It is not known whether NF-kappaB subunit composition changes during oncogenesis and regulates overall NF-kappaB activation. We compared the relative expression of NF-kappaB subunits with nuclear activation of p65 between variably differentiated pancreatic cancer cells. Materials and methods. Proliferating human pancreatic cancer cells (PANC-1, BxPC-3) and nonmalignant intestinal cells (FHS 74 Int) were harvested. Baseline expression of NF-kappaB subunits (p65, p52, p50, c-Rel) and its inhibitor lkappaB-alpha were determined by Western blot. Nuclear NF-kappaB p65 activity was measured by ELISA. Results were analyzed by ANOVA (P < 0.05) and Tukey's HSD for pairwise comparisons when appropriate (P < 0.05). Results. Constitutive expression of NF-kappaB subunits was detected in proliferating, intestinal cells (FHS 74 Int). Both cytoplasmic (licB-a, p50, p52, p65) and nuclear (p50, p52, p65, c-Rel) NF-kappaB subunits were significantly increased in both PANC-1 and BxPC-3 cells compared to FHS 74 Int. While nuclear p65 subunit levels were similarly elevated, actual p65 activity was only significantly greater in PANC-1 cells compared to either BxPC-3 or FHS 74 Int (P < 0.05). Conclusions. Compared to nonmalignant proliferating intestinal cells, these pancreatic cancer cell lines have increased levels of NF-kappaB subunits. Actual nuclear NF-kappaB activity, however, appears to correlate more with degree of tumor differentiation than with NF-kappaB subunit expression. (C) 2004 Elsevier Inc. All rights reserved.