Nuclear factor-κB activation and differential expression of survivin and Bcl-2 in human grade 2-4 astrocytomas

BACKGROUND. Antiapoptotis resulting from hyperactivation of the transcription factor NF-κB has been described in several cancer types. It is triggered by the interaction of the tumor necrosis factor (TNF) with its receptors and recruitment of the intermediate factor TNF-receptor associated factor (TRAF) 2. The NF-κB transcriptional activity could amplify the expression of antiapoptotic genes. The authors investigated the activity of NF-κB, and the mRNA expression of TNFα, TNFα receptor, TRAF1 TRAF2 and TRAF-associated NF-κB activator (TANK), and the antiapoptotic genes Bcl-2, c-IAP 1 and 2, and Survivin in human astrocytic tumors. METHODS. Eight low-grade astrocytomas (LGA), 10 anaplastic astrocytomas (AAs), 10 glioblastoma multiforme (GBM) samples were used; 4 samples of normal brain tissue were used as controls. The NF-κB activation was analyzed by electrophoretic mobility shift assay; TRAF1, TRAF2, TANK/I-TRAF, Bcl-2, c-IAP 1 and 2, and Survivin mRNA expressions were studied using real-time quantitative reverse-transcriptase polymerase chain reaction. RESULTS. NF-κB hyperactivity was detected in tumor samples. mRNA of antiapoptotic genes, particularly BCL-2 and Survivin, was hyperexpressed in gliomas. Interestingly, BCL-2 was hyperexpressed in LGAs, whereas a very high level of Survivin featured high-grade gliomas. The differential expression of antiapoptotic genes yielded a tight clustering of all LGA and nearly all GBM samples in cluster analysis. CONCLUSIONS. NF-κB and factors involved in its intracellular activation were up-regulated in gliomas. NF-κB-activated antiapoptotic genes were hyperexpressed in tumor samples, but showed a differential expression with higher levels of Bcl-2 in LGAs and higher levels of Survivin in GBMs. © 2008 American Cancer Society.