A regulatory network of canonical nuclear factor-κB activation predicts high-grade glioma outcome

2007 Background: The mechanism for decision between cell death and survival is under fine regulation. Nuclear factor-κB is a transcription regulator that is known to promote survival in many cellular events. Excessive and prolonged activation of NF-κB has been established as a principal mechanism of tumor chemoresistance, which is primarily mediated by its antiapoptotic activity. The pathway leading to the activation of NF-κB involves a complicated network that includes multiple modulatory signaling molecules. We have discovered alterations in several NF-κB pathway modulators in glioblastoma cells, which may act synergistically in activating NF-κB during resistance formation to O6-alkylating agents, including the TNFAIP3, NFKBIA, and TNIP1 genes. Methods: We have retrospectively evaluated the outcome relationship for these and additional endogenous inhibitors of canonical NF-κB activation in three independent high-grade glioma cohorts comprising 175 tumors. Results: We here confirmed the putative importan...