Burow M E, Weldon C B, Melnik L I, Duong B N, Collins-Burow B M, Beckman B S, McLachlan J A
Tulane-Xavier Center for Bioenvironmental Research, Department of Pharmacology, Tulane University Medical Center, New Orleans, LA 70112, USA.
Biochem Biophys Res Commun. 2000 May 10;271(2):342-5. doi: 10.1006/bbrc.2000.2626.
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-kappaB 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 well as a cell survival signal through NF-kappaB. PI3K and AKT cell survival signaling were correlated with increased TNF-stimulated NF-kappaB activity in MCF-7 cells. We demonstrate that while both TNFR1 and NIK are partially involved in Akt-induced NF-kappaB stimulation, a dominant negative IkappaBalpha completely blocked Akt-NF-kappaB cross-talk. PI3K-Akt signaling activated NF-kappaB through both TNFR signaling-dependent and -independent mechanisms, potentially representing a mechanism by which Akt functions to suppress apoptosis in cancer.
我们发现，在MCF-7乳腺癌细胞中，PI3K和Akt抑制肿瘤坏死因子α（TNF）诱导的剂量依赖性凋亡。PI3K和Akt以剂量依赖性方式刺激NF-κB激活，表明这两条途径之间存在共同联系。TNF已被证明既能激活凋亡级联反应，也能通过NF-κB激活细胞存活信号。PI3K和AKT细胞存活信号与MCF-7细胞中TNF刺激的NF-κB活性增加相关。我们证明，虽然TNFR1和NIK都部分参与Akt诱导的NF-κB刺激，但显性负性IκBα完全阻断了Akt与NF-κB的相互作用。PI3K-Akt信号通过TNFR信号依赖性和非依赖性机制激活NF-κB，这可能是Akt在癌症中发挥抑制凋亡作用的一种机制。
