Role of IκBα as a negative regulator of EGFR and a molecular determinant of prognosis in glioblastoma multiforme

2028 Background: Glioblastoma multiforme is a complex disease that involves the deregulation of overlapping signaling pathways. Constitutive activation of the transcription factor nuclear factor-κB (NF-κB) has been broadly associated with various human cancers, including glioblastomas, and their therapy resistance and may be due to cross-coupling with other oncogenic pathways, such as epidermal growth factor signaling. Methods: Multidimensional analysis involving gene and transcript data for the endogenous NF-κB modulator IκBα/NFKBIA and clinical patient profiles of 482 glioblastomas/high-grade gliomas from multiple institutions in the United States and The Cancer Genome Atlas Pilot Project. Functional analyses using LN229, U87, and U118 glioblastoma cells, and human embryonic kidney 293T cells with transgene phenotypes for IκBα. IκBα promoter and coding sequence and promoter methylation analyses in a resistance model of 15 glioblastomas cell lines with in vitro and/or in vivo resistance to O6-alkylating ...