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

• Published in: Cancer 2008-05, Vol.112 (10), p.2258-2266
• Main Authors: Angileri, Filippo F, Aguennouz, M'Hammed, Conti, Alfredo, La Torre, Domenico, Cardali, Salvatore, Crupi, Rosalia, Tomasello, Chiara, Germanò, Antonino, Vita, Giuseppe, Tomasello, Francesco
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adult; Aged; Astrocytoma - genetics; Astrocytoma - metabolism; Astrocytoma - pathology; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Case-Control Studies; Cell Differentiation; Electrophoretic Mobility Shift Assay; Female; Humans; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Male; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Staging; NF-kappa B - genetics; NF-kappa B - metabolism; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tankyrases - genetics; Tankyrases - metabolism; TNF Receptor-Associated Factor 1 - genetics; TNF Receptor-Associated Factor 1 - metabolism; TNF Receptor-Associated Factor 2 - genetics; TNF Receptor-Associated Factor 2 - metabolism
• ISSN: 0008-543X
• DOI: 10.1002/cncr.23407

Antiapoptotis resulting from hyperactivation of the transcription factor NF-kappaB 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-kappaB transcriptional activity could amplify the expression of antiapoptotic genes. The authors investigated the activity of NF-kappaB, and the mRNA expression of TNFalpha, TNFalpha receptor, TRAF1, TRAF2, and TRAF-associated NF-kappaB activator (TANK), and the antiapoptotic genes Bcl-2, c-IAP 1 and 2, and Survivin in human astrocytic tumors. 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-kappaB 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. NF-kappaB 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. NF-kappaB and factors involved in its intracellular activation were up-regulated in gliomas. NF-kappaB-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.