Conti Alfredo, Ageunnouz M'Hammed, La Torre Domenico, Cardali Salvatore, Angileri Filippo Flavio, Buemi Catia, Tomasello Chiara, Iacopino Domenico Gerardo, D'Avella Domenico, Vita Giuseppe, Tomasello Francesco
Department of Neuroscience, Neurosurgical and Neurological Clinics, University of Messina School of Medicine, Messina, Italy.
J Neurosurg. 2005 Nov;103(5):873-81. doi: 10.3171/jns.2005.103.5.0873.
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.
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).
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.
肿瘤坏死因子受体（TNFR）相关因子（TRAFs）是最近确定的一组参与TNFR超家族成员细胞内信号传导的蛋白质。TRAFs通过激活转录因子核因子（NF）-κB参与促进细胞存活。作者研究了NF-κB、半胱天冬酶3、TRAF1、TRAF2以及TRAF相关的NF-κB激活剂/TRAF相互作用蛋白（TANK/I-TRAF，一种TRAF活性调节剂）在人类胶质瘤中的表达。
获取了27例成年患者的肿瘤样本，其中包括7例低级别胶质瘤、9例间变性星形细胞瘤和11例多形性胶质母细胞瘤。使用电泳迁移率变动分析来分析NF-κB的激活情况；使用蛋白质印迹分析来研究TRAF1、TRAF2、TANK/I-TRAF和半胱天冬酶3的表达。与正常脑组织相比，在所有肿瘤样本中均检测到NF-κB DNA结合活性上调（p = 0.002）。NF-κB活性水平与世界卫生组织肿瘤分级存在一定相关性（p = 0.01），尽管由于组织异质性导致定量分析中有大量异常值，活性水平存在变化。与正常脑组织相比，星形细胞瘤中TRAF1、TRAF2和TANK/I-TRAF的表达水平升高（分别为p = 0.02、0.006和0.01）。
本研究数据证实了胶质瘤中NF-κB的上调，并揭示了该转录因子水平与肿瘤分级之间的相关性。记录了TRAF1、TRAF2和TANK/I-TRAF在人类胶质瘤中的组成性表达。这些蛋白质参与TNFR超家族的细胞内信号转导以及NF-κB表达及其抗凋亡活性的调控。
