Persistent inhibition of FLIP(L) expression by lentiviral small hairpin RNA delivery restores death-receptor-induced apoptosis in neuroblastoma cells.

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Serval ID
serval:BIB_C5974A0A7818
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Persistent inhibition of FLIP(L) expression by lentiviral small hairpin RNA delivery restores death-receptor-induced apoptosis in neuroblastoma cells.
Journal
Apoptosis : an international journal on programmed cell death
Author(s)
Flahaut M, Mühlethaler-Mottet A, Auderset K, Bourloud KB, Meier R, Popovic MB, Joseph JM, Gross N
Publication state
Published
Issued date
02/2006
Peer-reviewed
Oui
Language
english
Abstract
Neuroblastoma represents the most common and deadly solid tumour of childhood, which disparate biological and clinical behaviour can be explained by differential regulation of apoptosis. To understand mechanisms underlying death resistance in neuroblastoma cells, we developed small hairpin of RNA produced by lentiviral vectors as tools to selectively interfere with FLIPL, a major negative regulator of death receptor-induced apoptosis. Such tools revealed highly efficient in interfering with FLIPL expression and function as they almost completely repressed endogenous and/or exogenously overexpressed FLIPL protein and fully reversed FLIPL-mediated TRAIL resistance. Moreover, interference with endogenous FLIPL and FLIPS significantly restored FasL sensitivity in SH-EP neuroblastoma cell line. These results reveal the ability of lentivirus-mediated shRNAs to specifically and persistently interfere with FLIP expression and support involvement of FLIP in the regulation of death receptor-mediated apoptosis in neuroblastoma cells. Combining such tools with other therapeutic modalities may improve treatment of resistant tumours such as neuroblastoma.
Keywords
apoptosis, death receptors, FLIP, lentivirus-mediated shRNA, neuroblastoma
Pubmed
Create date
23/03/2020 12:44
Last modification date
24/03/2020 7:26
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