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Biochem Biophys Res Commun. 2000 May 10;271(2):342-5.

PI3-K/AKT regulation of NF-kappaB signaling events in suppression of TNF-induced apoptosis.

Author information

1
Tulane-Xavier Center for Bioenvironmental Research, Department of Pharmacology, Tulane University Medical Center, New Orleans, LA 70112, USA. mburow@tcs.tulane.edu

Abstract

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.

PMID:
10799299
DOI:
10.1006/bbrc.2000.2626
[Indexed for MEDLINE]

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