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Constitutively activated nuclear factor-κB, but not induced NF-κB, leads to TRAIL resistance by up-regulation of X-linked inhibitor of apoptosis protein in human cancer cells

Braeuer, SJ and Büneker, C and Mohr, A and Zwacka, RM (2006) 'Constitutively activated nuclear factor-κB, but not induced NF-κB, leads to TRAIL resistance by up-regulation of X-linked inhibitor of apoptosis protein in human cancer cells.' Molecular Cancer Research, 4 (10). 715 - 728. ISSN 1541-7786

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Abstract

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in most, but not all, cancer cells. The molecular factors regulating the sensitivity to TRAIL are still incompletely understood. The transcription factor nuclear factor-κB (NF-κB) has been implicated, but its exact role is controversial. We studied different cell lines displaying varying responses to TRAIL and found that TRAIL can activate NF-κB in all our cancer cell lines regardless of their TRAIL sensitivity. Inhibition of NF-κB via adenoviral expression of the IκB-α super-repressor only sensitized the TRAIL-resistant pancreatic cancer cell line Panc-1. Panc-1 cells harbor constitutively activated NF-κB, pointing to a possible role of preactivated NF-κB in protection from TRAIL. Furthermore, we could reduce X-linked inhibitor of apoptosis protein (XIAP) levels in Panc-1 cells by inhibition of constitutively activated NF-κB and sensitize Panc-1 cells to TRAIL by RNA interference against XIAP. These results implicate elevated XIAP levels caused by high basal NF-κB activity in TRAIL resistance and suggest that therapeutic strategies involving TRAIL can be abetted by inhibition of NF-κB and/or XIAP only in tumor cells with constitutively activated NF-κB. Copyright © 2006 American Association for Cancer Research.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 29 Jun 2017 10:14
Last Modified: 30 Jan 2019 16:15
URI: http://repository.essex.ac.uk/id/eprint/8329

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