High level of cFLIP correlates with resistance to death receptor-induced apoptosis in bladder carcinoma cells.
Anticancer Res. 2003 Mar-Apr; 23(2B):1213-8.AR

Abstract

BACKGROUND

The cellular form of FLICE-inhibitory protein (cFLIP) blocks death receptor-induced apoptosis and has been implicated in tumour progression. cFLIP interacts with caspase-8, thereby preventing activation of the caspase cascade. In this study we investigated the endogenous expression of cFLIP and caspase-8 in bladder carcinoma cells in relation to their sensitivity to death receptor-ligation.

MATERIALS AND METHODS

Apoptosis was induced by agonistic anti-CD95 mAbs or recombinant TRAIL and quantified by the TUNEL technique. The relative mRNA expression of cFLIP and caspase-8 was quantified by real-time PCR. Stable expression of cFLIP long (cFLIPL) was obtained by retroviral transduction.

RESULTS

The relative ratio of cFLIP and caspase-8 was directly correlated to resistance to anti-CD95 or TRAIL-mediated apoptosis. Overexpression of cFLIPL shifted the responsiveness towards resistant status.

CONCLUSION

cFLIP is an important determinant of susceptibility to death receptor-induced apoptosis in bladder carcinomas and could function as a prognostic marker for death receptor sensitivity in future immune therapy.

Links

clones/clone libraries

Authors+Show Affiliations

Jönsson G
Department of Immunology, Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden. gun@imm2.su.se
Paulie S
No affiliation info available
Grandien A
No affiliation info available

MeSH

Antibodies, MonoclonalApoptosisApoptosis Regulatory ProteinsCASP8 and FADD-Like Apoptosis Regulating ProteinCarcinomaCarrier ProteinsCaspase 8Caspase 9CaspasesDrug Resistance, NeoplasmEnzyme InductionGene Expression Regulation, NeoplasticHumansIn Situ Nick-End LabelingIntracellular Signaling Peptides and ProteinsJurkat CellsMembrane GlycoproteinsNeoplasm ProteinsRNA, MessengerReceptors, TNF-Related Apoptosis-Inducing LigandReceptors, Tumor Necrosis FactorTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alphaUrinary Bladder Neoplasmsfas Receptor

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12820373