Faculty Collaboration Database

c-FLIP confers resistance to FAS-mediated apoptosis in anaplastic large-cell lymphoma. Blood 2006 Mar 15;107(6):2544-7

Date

11/24/2005

Pubmed ID

16304056

DOI

10.1182/blood-2005-06-2601

Scopus ID

2-s2.0-33644774474 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

We hypothesized that inhibition of the FAS-mediated apoptosis pathway by FLICE-like inhibitory protein (c-FLIP) may contribute to oncogenesis in ALK+ anaplastic large-cell lymphoma (ALCL). Treatment with increasing concentrations of CH-11 (CD95/FAS agonistic antibody) had no effect on cell viability of 2 ALK+ ALCL cell lines, Karpas 299 and SU-DHL1, each expressing high levels of c-FLIP. However, inhibition of endogenous c-FLIP expression by specific c-FLIP siRNA in Karpas 299 and SU-DHL1 cells treated with CH-11 resulted in FAS-mediated cell death associated with increased annexin V binding, apoptotic morphology, and cleavage of caspase-8. In 26 ALK+ ALCL tumors, assessed for expression of DISC-associated proteins, CD95/FAS and c-FLIP were commonly expressed, in 23 (92%) of 25 and 21 (91%) of 23 tumors, respectively. By contrast, CD95L/FASL was expressed in only 3 (12%) of 26 ALCL tumors, although it was strongly expressed by surrounding small reactive lymphocytes. Our findings suggest that overexpression of c-FLIP protects ALK+ ALCL cells from death-receptor-induced apoptosis and may contribute to ALCL pathogenesis.

Author List

Oyarzo MP, Medeiros LJ, Atwell C, Feretzaki M, Leventaki V, Drakos E, Amin HM, Rassidakis GZ

MESH terms used to index this publication - Major topics in bold

Annexin A5
Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein
Caspase 8
Caspases
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Humans
Intracellular Signaling Peptides and Proteins
Lymphoma, Large-Cell, Anaplastic
RNA, Small Interfering
fas Receptor