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Nuclear factor‐κB activation and differential expression of survivin and Bcl‐2 in human grade 2–4 astrocytomas
Author(s) -
Angileri Filippo F.,
Aguennouz M'Hammed,
Conti Alfredo,
La Torre Domenico,
Cardali Salvatore,
Crupi Rosalia,
Tomasello Chiara,
Germanò Antonino,
Vita Giuseppe,
Tomasello Francesco
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23407
Subject(s) - survivin , tumor necrosis factor alpha , cancer research , activator (genetics) , transcription factor , cd30 , glioma , gene expression , gene , microbiology and biotechnology , receptor , medicine , cancer , biology , immunology , tumor cells , biochemistry
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. Cancer 2008. © 2008 American Cancer Society.