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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
Author(s) -
Andela Valentine B.,
Schwarz Edward M.,
O'Keefe Regis J.,
Puzas Edward J.,
Rosenblatt Joseph D.,
Rosier Randy N.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.11.018
Subject(s) - downregulation and upregulation , cell culture , biology , microbiology and biotechnology , gene expression , reactive oxygen species , oxidative phosphorylation , gene , cancer research , biochemistry , genetics
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.