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
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
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