A genome-wide expression profile and system-level integration of nuclear factor kappa B regulated genes reveals fundamental metabolic adaptations during cell growth and survival

A murine lung alveolar carcinoma cell line (WT-Line 1) and its equally tumorigenic but non-malignant derivative transduced with a dominant negative inhibitor of NF-kappa B (mI-kappa B-Line 1), were profiled on the Affymetrix (R) 19000 gene array platform. Two differentially expressed gene clusters were identified and integrated into a functional model. The down-regulation of anti-oxidant defenses, in mI-kappa B-Line 1 cells, correlates with high levels of reactive oxygen species (ROS) and ROS damage to cellular macromolecules while the up-regulation of metabolic nuclear receptors correlates with an adaptive/survival response, which involves a shift in energy metabolism toward beta-oxidative respiration. Accordingly, mI-kappa B-Line 1 cells are markedly sensitized to pharmacologic inhibition of beta-oxidative respiration. These findings are indicative of compensatory changes that could undermine anti-cancer therapies targeting NF-kappa B. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.