Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

Details

Serval ID
serval:BIB_B01383921A13
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis
Journal
Cancer Research
Author(s)
Hopkins-Donaldson  S., Bodmer  J. L., Bourloud  K. B., Brognara  C. B., Tschopp  J., Gross  N.
ISSN
0008-5472 (Print)
Publication state
Published
Issued date
08/2000
Volume
60
Number
16
Pages
4315-9
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 15
Abstract
Human neuroblastoma (NB) is a highly heterogeneous childhood cancer that is aggressively malignant or can undergo spontaneous regression that may involve apoptosis. NB-derived cell lines were tested for their sensitivity to apoptosis induced by the tumor-selective ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Noninvasive S-type cell lines (NB cell lines of substrate adherent phenotype) are highly sensitive to TRAIL, whereas invasive N-type cell lines (NB cell lines of neuronal phenotype) are resistant. Whereas both S- and N-type cell lines express TRAIL-R2, FADD, and caspase-3 and -10, only S-type cells express caspase-8. Reduced levels of caspase-8 protein were also observed in a malignant stage IV NB tumor when compared with a benign ganglioneuroma. The caspase-8 gene is not deleted in either N-type NB cell lines or high-stage NB tumors. Caspase-8 expression can be induced by demethylation with 5-aza-2'deoxycytidine, which enhances sensitivity to TRAIL. Therefore, caspase-8 expression is silenced in malignant NB, which correlates to tumor severity and resistance to TRAIL-induced apoptosis.
Keywords
Animals Apoptosis/drug effects/*physiology Apoptosis Regulatory Proteins Caspase 3 Caspase 8 Caspase 9 Caspases/*biosynthesis/metabolism Enzyme Activation Fas Ligand Protein Ganglioneuroma/enzymology/pathology Humans Immunohistochemistry Membrane Glycoproteins/*pharmacology Neoplasm Invasiveness Neoplasm Staging Neural Cell Adhesion Molecules/biosynthesis/physiology Neuroblastoma/*enzymology/pathology Phenotype Rabbits Receptors, Tumor Necrosis Factor/biosynthesis/physiology Recombinant Proteins/pharmacology TNF-Related Apoptosis-Inducing Ligand Tumor Cells, Cultured Tumor Necrosis Factor-alpha/*pharmacology
Pubmed
Web of science
Create date
24/01/2008 16:19
Last modification date
20/08/2019 16:19
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