Induction of p21Waf1/Cip1 by TNFα requires NF-κB activity and antagonizes apoptosis in Ewing tumor cells
作者： Delphine Javelaud , Juana Wietzerbin , Olivier Delattre , Françoise Besançon
关键词: Carcinogenesis 、 Biology 、 Cancer research 、 Tumor necrosis factor alpha 、 Cell culture 、 Ewing family of tumors 、 Cytokine 、 NF-κB 、 Fusion protein 、 IκBα
摘要: The Ewing family of tumors is characterized by recurrent reciprocal translocations that generate chimeric proteins, either EWS–FLI-1 or EWS–ERG. These proteins are potent transcriptional activators and responsible for maintaining the oncogenic properties tumor cells. Since apoptosis appears to be main mechanism whereby chemotherapy radiation kill cells, identification events can antagonize in essential improving their response conventional therapies. Here, we report factor NF-κB a survival tumor-derived In fact, inhibition activation as consequence overexpression degradation-resistant form IκBα, IκBα (A32/36), sensitized these cells TNFα-induced killing. Although treatment with TNFα did not modify cellular expression Bcl-2, c-IAP1, c-IAP2, p53 it increased p21Waf1/Cip1 levels. This induction required since was observed (A32/36) expressing Moreover, (A32/36)-expressing which consequently no longer inducible TNFα, decreased susceptibility Our results therefore identify mediator antiapoptotic effect
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