PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-κB signaling pathway in human glioma cells
PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-κB signaling pathway in human glioma cells
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DOI：
10.1016/j.bbrc.2006.09.077
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发表时间：
2006-11-17
影响因子：
3.1
通讯作者：
Yung, W. K. Alfred
中科院分区：
文献类型：
--
作者：
Koul, Dimpy;Takada, Yasunari;Yung, W. K. Alfred
PTEN肿瘤抑制基因调节细胞生长和存活，已知其通过转录因子NF κ B的活化来调节。提示PTEN可能影响NF κ B B活化途径。我们发现，PTEN抑制TNF诱导的NF κ B B活化。NF κ B B活化的抑制与肿瘤坏死因子诱导的NF κ B调节的抗凋亡（IAP 1、IAP 2、Bcl-2、Bcl-xL、cFLIP、Bfl-1/A1和生存素）基因产物表达的顺序抑制相关。如半胱天冬酶激活、TUNEL、膜联蛋白染色和酯酶测定所示，PTEN下调抗凋亡基因增加TNF诱导的细胞凋亡。我们的结论是，异位表达的PTEN增强肿瘤坏死因子诱导的细胞凋亡和下调神经胶质瘤细胞的增殖，通过抑制各种分子，包括NF κ B B，和各种介质的细胞生存和增殖，这可能是必不可少的目标，其核心作用在神经胶质瘤癌细胞的生长和生存。(c)2006年爱思唯尔公司All rights reserved.
The PTEN tumor suppressor gene modulates cell growth and survival known to be regulated by the activation of the transcription factor NF kappa B. suggesting PTEN might affect the NF kappa B activation pathway. We found that PTEN inhibited NF kappa B activation induced by TNF. The suppression of NF kappa B activation correlated with sequential inhibition of the tumor necrosis factor-induced expression of NF kappa B-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin) gene products. Downregulation of the antiapoptotic genes by PTEN increased TNF-induced apoptosis, as indicated by caspase activation, TUNEL, annexin staining, and esterase assay. We conclude that the ectopic expression of PTEN enhances TNF-induced apoptosis and downregulates the proliferation of glioma cells through the suppression of various molecules including NF kappa B, and various mediators of cellular survival and proliferation, and that this targets might be essential for its central role in the growth and survival of glioma cancer cells. (c) 2006 Elsevier Inc. All rights reserved.