ORBi: Benoit Valérie - Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappa B through c-FLIP-L expression

Reference : Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulatio...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/2268/1464

Title :	Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappa B through c-FLIP-L expression
Language :	English
Author, co-author :	Benoit, Valérie [> > > >]
	Chariot, Alain [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
	Delacroix, Laurence [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
	Deregowski, Valérie [> > > >]
	Jacobs, Nathalie [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
	Merville, Marie-Paule [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
	Bours, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Publication date :	2004
Journal title :	Cancer Research
Publisher :	Amer Assoc Cancer Research
Volume :	64
Issue/season :	8
Pages :	2684-2691
Audience :	International
ISSN :	0008-5472
e-ISSN :	1538-7445
City :	Philadelphia
Country :	USA
Keywords :	[en] Adenocarcinoma/enzymology/metabolism/pathology ; Anti-Infective Agents/pharmacology ; Apoptosis/physiology ; Binding Sites ; Breast Neoplasms/enzymology/metabolism/pathology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; Carrier Proteins/metabolism ; Caspase 8 ; Caspases/antagonists & inhibitors/metabolism ; Cell Line, Tumor ; Cycloheximide/pharmacology ; HER-2 ; Intracellular Signaling Peptides and Proteins ; MCF7 ; NF kappa B ; Sulfones ; Transcriptional Activation ; Tumor Necrosis Factor-alpha/pharmacology
Abstract :	[en] The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and that tumor necrosis factor alpha (TNF-alpha) stimulation leads to an early caspase-8-dependent HER-2 cleavage in MCF7 A/Z breast adenocarcinoma cells defective for nuclear factor kappaB (NFkappaB) activation. We show that the antiapoptotic transcription factor NFkappaB counteracts this cleavage through induction of the caspase-8 inhibitor c-FLIP. Our results also demonstrate that this HER-2 cleavage contributes to the TNF-alpha-induced apoptosis pathway because ectopic expression of an uncleavable HER-2 protects NFkappaB-defective cells against TNF-alpha-mediated cell death. Therefore, we propose an original model in which NFkappaB exerts a new antiapoptotic function by counteracting TNF-alpha-triggered cleavage of the HER-2 survival factor.
Research units :	Giga-Signal Transduction
Funders :	Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; TELEVIE, ARC ULG
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/2268/1464
	also: http://hdl.handle.net/2268/105340

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