BACKGROUND: Activation of NF-kappa B-dependent antiapoptotic genes may factor in the chemoresistance of pancreatic cancer. It is not known whether NF-kappa B subunit composition changes during oncogenesis and regulates overall NF-kappa B activation. We compared the relative expression of NF-kappa B 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-kappa B subunits (p65, p52, p50, c-Rel) and its inhibitor I kappa B-alpha were determined by Western blot. Nuclear NF-kappa B 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-kappa B subunits was detected in proliferating, intestinal cells (FHS 74 Int). Both cytoplasmic (I kappa B-alpha, p50, p52, p65) and nuclear (p50, p52, p65, c-Rel) NF-kappa B 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-kappa B subunits. Actual nuclear NF-kappa B activity, however, appears to correlate more with degree of tumor differentiation than with NF-kappa B subunit expression.
BACKGROUND: Activation of NF-kappa B-dependent antiapoptotic genes may factor in the chemoresistance of pancreatic cancer. It is not known whether NF-kappa B subunit composition changes during oncogenesis and regulates overall NF-kappa B activation. We compared the relative expression of NF-kappa B subunits with nuclear activation of p65 between variably differentiated pancreatic cancer cells. MATERIALS AND METHODS: Proliferating humanpancreatic cancer cells (PANC-1, BxPC-3) and nonmalignant intestinal cells (FHS 74 Int) were harvested. Baseline expression of NF-kappa B subunits (p65, p52, p50, c-Rel) and its inhibitor I kappa B-alpha were determined by Western blot. Nuclear NF-kappa Bp65 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-kappa B subunits was detected in proliferating, intestinal cells (FHS 74 Int). Both cytoplasmic (I kappa B-alpha, p50, p52, p65) and nuclear (p50, p52, p65, c-Rel) NF-kappa B 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-kappa B subunits. Actual nuclear NF-kappa B activity, however, appears to correlate more with degree of tumor differentiation than with NF-kappa B subunit expression.
Authors: Joerg Schreiber; Richard G Jenner; Heather L Murray; Georg K Gerber; David K Gifford; Richard A Young Journal: Proc Natl Acad Sci U S A Date: 2006-04-04 Impact factor: 11.205
Authors: Bilal Bin Hafeez; Ala Mustafa; Joseph W Fischer; Ashok Singh; Weixiong Zhong; Mohammed Ozair Shekhani; Louise Meske; Thomas Havighurst; KyungMann Kim; Ajit Kumar Verma Journal: Antioxid Redox Signal Date: 2014-02-06 Impact factor: 8.401
Authors: Prakash Radhakrishnan; Vashti C Bryant; Elizabeth C Blowers; Rajkumar N Rajule; Nagsen Gautam; Muhammad M Anwar; Ashley M Mohr; Paul M Grandgenett; Stephanie K Bunt; Jamie L Arnst; Subodh M Lele; Yazen Alnouti; Michael A Hollingsworth; Amarnath Natarajan Journal: Clin Cancer Res Date: 2013-02-26 Impact factor: 12.531