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

作者：Angileri Filippo F; Aguennouz M'Hammed; Conti Alfredo^*; La Torre Domenico; Cardali Salvatore; Crupi Rosalia; Tomasello Chiara; Germano Antonino; Vita Giuseppe; Tomasello Francesco

来源：Cancer, 2008, 112(10): 2258-2266.

DOI：10.1002/cncr.23407

• nuclear factor-kappa B
• tumor necrosis factor
• Bcl-2
• survivin
• glioma

BACKGROUND. Antiapoptotis resulting from hyperactivation of the transcription factor NF-kappa beta 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-kappa B transcriptional activity could amplify the expression of antiapoptotic genes. The authors investigated the activity of NF-kappa B, and the mRNA expression of TNF alpha, TNF alpha receptor, TRAF1, TRAF2, and TRAF-associated NF-kappa B 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-kappa B 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-kappa B hyperactivity was detected in tumor samples. mRNA of antia-poptotic 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-kappa B and factors involved in its intracellular activation were up-regulated in gliomas. NF-kappa B-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.

• 出版日期2008-5-15