Nuclear factor-kappaB 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-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.


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-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.


RESULTS
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.


CONCLUSIONS
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.
Angileri
Filippo F
FF
Department of Neuroscience, University of Messina School of Medicine, Messina, Italy.
Aguennouz
M'Hammed
M
Conti
Alfredo
A
La Torre
Domenico
D
Cardali
Salvatore
S
Crupi
Rosalia
R
Tomasello
Chiara
C
Germanò
Antonino
A
Vita
Giuseppe
G
Tomasello
Francesco
F
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism; D038501:Tankyrases / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000077022:Survivin; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D038501:Tankyrases; C107489:BIRC5 protein, human; C484406:TANK protein, human; C418109:TNKS protein, human