PI3-K/AKT regulation of NF-κB signaling events in suppression of TNF-induced apoptosis
PI3-K/AKT regulation of NF-κB signaling events in suppression of TNF-induced apoptosis
复制标题
DOI：
10.1006/bbrc.2000.2626
复制
发表时间：
2000-05-10
影响因子：
3.1
通讯作者：
McLachlan, JA
中科院分区：
文献类型：
--
作者：
Burow, ME;Weldon, CB;McLachlan, JA
我们发现，在MCF-7乳腺癌细胞中，PI 3 K和Akt抑制肿瘤坏死因子α（TNF）诱导凋亡的剂量依赖性。PI 3 K和Akt以剂量依赖性方式刺激NF-κ B B活化，表明这两种途径之间存在共同联系。TNF已经显示激活凋亡级联，以及通过NF-κ B的细胞存活信号。在MCF-7细胞中，PI 3 K和ART细胞存活信号与TNF刺激的NF-κ B活性增加相关。我们证明，虽然TNFR 1和NIK都部分参与Akt诱导的NF-κ B刺激，但显性负性I κ B α完全阻断了Akt-NF-κ B串扰。PI 3 K-Akt信号通过TNFR信号依赖性和非依赖性机制激活NF-κ B B，可能代表Akt在癌症中抑制细胞凋亡的机制。(C)北京大学出版社.
We found that in MCF-7 breast carcinoma cells, PI3K and Akt suppressed a dose-dependent induction of apoptosis by tumor necrosis factor alpha (TNF). PI3K and Akt stimulated NF-kappa B activation in a dose-dependent manner, suggesting a common link between these two pathways. TNF has been shown to activate both an apoptotic cascade, as web as a cell survival signal through NF-kappa B. PI3K and ART cell survival signaling were correlated with increased TNF-stimulated NF-kappa B activity in MCF-7 cells. We demonstrate that while both TNFR1 and NIK are partially involved in Akt-induced NF-kappa B stimulation, a dominant negative I kappa B alpha completely blocked Akt-NF-kappa B cross-talk. PI3K-Akt signaling activated NF-kappa B through both TNFR signaling-dependent and -independent mechanisms, potentially representing a mechanism by which Akt functions to suppress apoptosis in cancer. (C) 2000 Academic Press.