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IKBKE is over‐expressed in glioma and contributes to resistance of glioma cells to apoptosis via activating NF‐κB
Author(s) -
Guan Hongyu,
Zhang Heng,
Cai Junchao,
Wu Jueheng,
Yuan Jie,
Li Jun,
Huang Zhengsong,
Li Mengfeng
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2815
Subject(s) - biology , glioma , iκb kinase , cancer research , nf κb , signal transduction , microbiology and biotechnology
IκB kinase‐ε (IKBKE), a member of the IκB kinase (IKK) family, has been identified as an oncogenic protein and found to be up‐regulated in breast cancer, ovarian cancer and prostate cancer. Nonetheless, the expression status and functional significance of IKBKE in human glioma remain unexplored. For the first time, we have demonstrated that mRNA and protein levels of IKBKE were robustly up‐regulated in glioma cell lines and human primary glioma tissues. Immunohistochemistry analysis revealed that 53.5% (38/71) paraffin‐embedded archived glioma specimens exhibited high levels of IKBKE expression. Intriguingly, there was no significant difference in IKBKE expression among different grades of glioma. To understand the biological function of IKBKE in the development and progression of human glioma, glioma cells lines ectopically over‐expressing IKBKE were established and tested for their responsiveness to apoptotic inducers. Our data showed that IKBKE over‐expression inhibited cell apoptosis induced by UV irradiation or adriamycin and, in contrast, shRNAi‐mediated suppression of IKBKE increased the sensitivity of glioma cells to the apoptotic inducers. Importantly, we found that up‐regulated IKBKE could induce the expression of Bcl‐2 through activating NF‐κB signalling, and that, specifically, we identified IκB as a critical component for this signalling cascade. The current study suggests that up‐regulation of IKBKE may represent an important molecular hallmark that is biologically and clinically relevant to the development and progression, as well as the chemo‐ and radio‐resistance, of the disease. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.