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

Valentine B. Andela, Edward M. Schwarz, Regis J. O'Keefe, Edward J. Puzas, Joseph D. Rosenblatt, Randy N. Rosier

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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-κB (mI-κB-Line 1), were profiled on the Affymetrix® 19 000 gene array platform. Two differentially expressed gene clusters were identified and integrated into a functional model. The downregulation of anti-oxidant defenses, in mI-κB-Line 1 cells, correlates with high levels of reactive oxygen species (ROS) and ROS damage to cellular macromolecules while the upregulation of metabolic nuclear receptors correlates with an adaptive/survival response, which involves a shift in energy metabolism toward β-oxidative respiration. Accordingly, mI-κB-Line 1 cells are markedly sensitized to pharmacologic inhibition of β-oxidative respiration. These findings are indicative of compensatory changes that could undermine anti-cancer therapies targeting NF-κB.

Original languageEnglish (US)
Pages (from-to)6814-6820
Number of pages7
JournalFEBS letters
Volume579
Issue number30
DOIs
StatePublished - Dec 19 2005

Keywords

  • β-Oxidation
  • Apoptosis
  • Glycolysis
  • NF-κB
  • Oxidative stress
  • Survival

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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