IκBζ, an Atypical Member of the Inhibitor of Nuclear Factor Kappa B Family, Is Induced by γ-Irradiation in Glioma Cells, Regulating Cytokine Secretion and Associated With Poor Prognosis

Abstract

The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is associated with poor prognosis. Here we report that IκBζ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBζ expression is enhanced, and subsequently serves as a transcriptional activator of the tumor promoting cytokines interleukin (IL-6), IL-8 and chemokine (C-X-C motif) ligand 1 (CXCL1) that are known to be involved in glioma associated inflammatory processes. In contrast, shRNA-mediated knockdown of IκBζ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBζ in the inflammatory micromilieu as well as progression in glioma.

Publication
In Int J Oncol, 47 (5), 1971-80, Nov 2015
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Heiko Brennenstuhl
Medical Professional, MBA & Postdoctoral Research Fellow

I am interested in inherited metabolic disorders and neurosmuscular diseases with a movement pehnotype. I specialize in stem cell research and challenges and opportunities of high-throughput data analysis.