title: Expression of short-form caspase 8 correlates with decreased sensitivity to Fas-mediated apoptosis in neuroblastoma cells.
abstract: Disruption of apoptotic death signal transduction pathways may be responsible for tumor formation, progression and resistance to treatment in neuroblastoma. Caspase 8, one of the initiator caspases, plays an important role in the Fas-Fas ligand pathway. This caspase signals through the formation of a death-inducing signaling complex in response to Fas activation by its ligand. In this study, we evaluated the sensitivity of a series of human neuroblastoma cell lines to membrane-bound Fas ligand induced-cell death, as well as the expression of Fas, caspase 3 and caspase 8. Sensitivity to Fas-mediated cell death did not correlate with the expression of Fas in neuroblastoma cells, but was directly associated with the pattern of caspase 8 protein expression. We found that the majority of neuroblastoma cell lines we evaluated lacked caspase 8 expression, and these cell lines were invariably resistant to Fas-mediated cell death. In contrast, cell lines expressing normal caspase 8 protein were quite sensitive to Fas-mediated cell death. More interestingly, a group of cell lines expressing a distinct short form of caspase 8 with splicing out of exon 3 consistently showed moderate sensitivity to Fas-mediated cell death. These results indicate that the profile of caspase 8 expression is an important determinant of the response of neuroblastoma cells to Fas-mediated cell death.
authors.affiliation: Department of Pediatrics, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Rodrick R
authors.initials: RR
authors.lastname: Kisenge
authors.forename: Hidemi
authors.initials: H
authors.lastname: Toyoda
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Azuma
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007951:Leukemia, Myeloid; D009447:Neuroblastoma; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases