Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-κB pathway

Jun Li, Li Yun Gong, Li Bing Song, Li Li Jiang, Li Ping Liu, Jueheng Wu, Jie Yuan, Jun Chao Cai, Mian He, Lan Wang, Musheng Zeng, Shi Yuan Cheng*, Mengfeng Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

One of the features of malignant gliomas is their deviant resistance to cellular apoptosis induced by cytotoxic reagents. Bmi-1, an oncoprotein, has been linked to oncogenesis and cancer progression in various types of human cancers including gliomas. However, the mechanisms underlying Bmi-1 antiapoptotic function remain largely unknown. In this study, we report that Bmi-1 renders apoptotic resistance to glioma cells through nuclear factor-κB (NF-κB). In glioma cells, ectopic expression of Bmi-1 significantly inhibits doxorubicin-, BCNU-, or UV irradiationinduced apoptosis through reduction of activated caspase-3 and PARP, and induction of Bcl-X L. Cellular depletion of Bmi-1 enhances the sensitivity of glioma cells to apoptosis induced by doxorubicin, BCNU, or UV irradiation. Bmi-1 activates NF-κB through stimulation of IκB phosphorylation, nuclear translocation, and transcriptional activity of NF-κB and expression of downstream genes of NF-κB including caspase-3, PARP, Bcl-XL, and c-Myc. Inhibition of the IKK-NF-κB pathway abrogates the antiapoptotic effect of Bmi-1 on glioma cells. In high-grade gliomas, Bmi-1 and NF-κB are co-expressed in the cell nucleus. Up-regulation of Bmi-1 also correlates with tumor progression and poor survival of patients with gliomas. Together, our data demonstrate that Bmi-1 bestows apoptotic resistance to glioma cells through the IKKNF-κB pathway and suggest Bmi-1 as a useful indicator for glioma prognosis.

Original languageEnglish (US)
Pages (from-to)699-709
Number of pages11
JournalAmerican Journal of Pathology
Volume176
Issue number2
DOIs
StatePublished - Feb 2010

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-κB pathway'. Together they form a unique fingerprint.

Cite this