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Expression of the tumor necrosis factor
receptor-associated factors 1 and 2 and regulation of the nuclear
factor-kappaB antiapoptotic activity in human gliomas
Conti A, Ageunnouz M, La Torre D, Cardali S,
Angileri FF, Buemi C, Tomasello C, Iacopino DG,
D'Avella D, Vita G, Tomasello F.
Department of Neuroscience, Neurosurgical and Neurological Clinics,
University of Messina School of Medicine, Messina, Italy.
alfredo.conti@unime.it
Object. Tumor necrosis factor receptor (TNFR)-associated
factors (TRAFs) are a recently established group of proteins involved
in the intracellular signaling of the TNFR superfamily members.
The TRAFs have been implicated in promoting cell survival through the
activation of transcription factor nuclear factor (NF)-kappaB.
The authors investigated the expression of NF-kappaB, caspase 3,
TRAF1, TRAF2, and TRAF-associated NF-kappaB activator/TRAF-interacting
protein (TANK/I-TRAF), a regulator of TRAF activity, in human
gliomas.
Methods. Tumor samples
were obtained in 27 adult patients harboring seven low-grade gliomas,
nine anaplastic astrocytomas, and 11 glioblastomas multiforme.
The NF-kappaB activation was analyzed using the electrophoresis
mobility shift assay; TRAF1, TRAF2, TANK/I-TRAF, and caspase 3
expression were studied using Western blot analysis.
Upregulated NF-kappaB DNA-binding activity, compared with that in
normal brain tissue, was detected in all tumor samples (p =
0.002).
The level of NF-kappaB activity showed some correlation with World
Health Organization tumor grades (p = 0.01), even though variable
activity levels were demonstrated in relation to tissue heterogeneity,
which resulted in a substantial number of outliers in the quantitative
analysis.
Increased levels of TRAF1, TRAF2, and TANK/ I-TRAF were expressed in
astrocytomas compared with levels in normal brain tissue (p = 0.02,
0.006, and 0.01, respectively).
Conclusions. Data in this
study confirm the upregulation of NF-kappaB in gliomas and reveal a
correlation between levels of this transcription factor and tumor
grade.
A constitutive expression of TRAF1, TRAF2, and TANK/I-TRAF in human
gliomas was documented.
These proteins are involved in the intracellular signal transduction
of the TNFR superfamily and in the control of NF-kappaB expression and
its antiapoptotic activity.
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