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PMID: 11943736 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Constitutive expression of c-FLIP in Hodgkin and Reed-Sternberg cells.

The American journal of pathology ·Vol. 160 ·No. 4 ·2002-04-00 ·Pages 1521-8

Thomas RK, Kallenborn A, Wickenhauser C, Schultze JL, Draube A, Vockerodt M, Re D, Diehl V, Wolf J

Abstract

Crosslinking of the transmembrane receptor CD95/Fas leads to activation of a signaling cascade resulting in apoptosis. c-FLIP is a recently described protein that potently inhibits Fas-mediated apoptosis and has been shown to be a key factor in germinal center B cell survival. Because Hodgkin and Reed-Sternberg cells in classical Hodgkin's disease (cHD) are also resistant to Fas-mediated apoptosis we studied the role of c-FLIP in classical HD. High levels of c-FLIP protein were identified in two Fas-resistant Hodgkin-derived cell lines. In contrast to other tumor cells, inhibition of protein synthesis by cycloheximide did not lead to down-regulation of c-FLIP protein in these HD cell lines. Furthermore, Fas-mediated apoptosis was only partially restored suggesting that normal regulation of c-FLIP was disrupted. The in vivo relevance of these findings was supported by demonstration of significant c-FLIP expression by immunohistochemistry in 18 of 19 evaluable cases of primary HD. Taken together, c-FLIP is constitutively expressed in HD and may therefore be a major mechanism responsible for Fas-resistance in HD.

MeSH Terms
Adolescent Adult Aged Apoptosis/physiology CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins/genetics,metabolism Cycloheximide/pharmacology Down-Regulation Hodgkin Disease/metabolism,pathology,physiopathology Humans Intracellular Signaling Peptides and Proteins Middle Aged Protein Synthesis Inhibitors/pharmacology RNA, Messenger/metabolism Reed-Sternberg Cells/metabolism,physiology Tumor Cells, Cultured fas Receptor/physiology
Chemicals
CASP8 and FADD-Like Apoptosis Regulating Protein CFLAR protein, human Carrier Proteins Intracellular Signaling Peptides and Proteins Protein Synthesis Inhibitors RNA, Messenger fas Receptor Cycloheximide
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Thomas Roman Kurt
Department of Internal Medicine I, University of Cologne, Cologne, Germany.
Kallenborn Anne
Wickenhauser Claudia
Schultze Joachim Ludwig
Draube Andreas
Vockerodt Martina
Re Daniel
Diehl Volker
Wolf Jürgen
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)62578-3
Published
2002-04-00
Pages
1521-8
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1867202
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)62578-3 PMC Full Text View journal details
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