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Caspase 8L, a novel inhibitory isoform of caspase 8, is associated with undifferentiated neuroblastoma

Caspase 8 is a key apoptotic factor in the receptor/ligand apoptosis-signaling cascade. Absent caspase 8 expression is shown to correlate with poor prognosis in neuroblastoma. Paradoxically, the caspase 8 gene can produce as plice variant and novel inhibitor of itself-caspase 8l. The presence of cas... Full description

Journal Title: Apoptosis (London) 2006-01, Vol.11 (1), p.15-24
Main Author: Miller, M A
Other Authors: Karacay, B , Zhu, X , O'Dorisio, M S , Sandler, A D
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Netherlands: Springer
ID: ISSN: 1360-8185
Link: https://www.ncbi.nlm.nih.gov/pubmed/16374545
Zum Text:
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recordid: cdi_proquest_miscellaneous_70725719
title: Caspase 8L, a novel inhibitory isoform of caspase 8, is associated with undifferentiated neuroblastoma
format: Article
creator:
  • Miller, M A
  • Karacay, B
  • Zhu, X
  • O'Dorisio, M S
  • Sandler, A D
subjects:
  • Alternative Splicing
  • Apoptosis
  • Apoptosis - drug effects
  • Apoptosis - physiology
  • Base Sequence
  • Caspase 8 - genetics
  • Caspase 8 - metabolism
  • Caspase Inhibitors
  • Caspase-8
  • Cell death
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell lines
  • Cell Survival - physiology
  • Cloning, Molecular
  • DNA Primers - genetics
  • Etoposide
  • Gene Expression
  • Humans
  • Isoenzymes - antagonists & inhibitors
  • Isoenzymes - genetics
  • Isoenzymes - metabolism
  • Neuroblastoma
  • Neuroblastoma - enzymology
  • Neuroblastoma - genetics
  • Neuroblastoma - pathology
  • Overexpression
  • Phenotype
  • Phenotypes
  • Prognosis
  • TNF-Related Apoptosis-Inducing Ligand - pharmacology
  • TRAIL protein
  • Transfection
  • Tumors
ispartof: Apoptosis (London), 2006-01, Vol.11 (1), p.15-24
description: Caspase 8 is a key apoptotic factor in the receptor/ligand apoptosis-signaling cascade. Absent caspase 8 expression is shown to correlate with poor prognosis in neuroblastoma. Paradoxically, the caspase 8 gene can produce as plice variant and novel inhibitor of itself-caspase 8l. The presence of caspase 8 alone in tumors may not necessarily portend a good prognosis. We sought to determine whether caspase 8l is present in neuroblastoma and whether over-expression of this protein could inhibit caspase 8-dependent apoptosis. Six of 6 histologically undifferentiated and 2 of 5 differentiated neuroblastoma tumors expressed the caspase 8l isoform, whereas caspase 8l was absent in 3 of 3 ganglioneuromas. Seven human neuroblastoma cell lines were surveyed. Two of the 5 cell lines that expressed caspase 8 also expressed the caspase 8l isoform and both were of a less differentiated neuronal phenotype. Over-expression of caspase 8l in cell lines afforded protection against TRAIL, but not against etoposide induced apoptosis. Conversely, blockade of Caspase 8l in cells that express this splice variant made them more sensitive to apoptosis induced cell death. We demonstrate the caspase 8l isoform is present in neuroblastoma and appears to be associated with undifferentiated cell lines and tumors. Furthermore, it suppresses caspase 8-dependent apoptosis.
language: eng
source:
identifier: ISSN: 1360-8185
fulltext: no_fulltext
issn:
  • 1360-8185
  • 1573-675X
url: Link


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titleCaspase 8L, a novel inhibitory isoform of caspase 8, is associated with undifferentiated neuroblastoma
creatorMiller, M A ; Karacay, B ; Zhu, X ; O'Dorisio, M S ; Sandler, A D
creatorcontribMiller, M A ; Karacay, B ; Zhu, X ; O'Dorisio, M S ; Sandler, A D
descriptionCaspase 8 is a key apoptotic factor in the receptor/ligand apoptosis-signaling cascade. Absent caspase 8 expression is shown to correlate with poor prognosis in neuroblastoma. Paradoxically, the caspase 8 gene can produce as plice variant and novel inhibitor of itself-caspase 8l. The presence of caspase 8 alone in tumors may not necessarily portend a good prognosis. We sought to determine whether caspase 8l is present in neuroblastoma and whether over-expression of this protein could inhibit caspase 8-dependent apoptosis. Six of 6 histologically undifferentiated and 2 of 5 differentiated neuroblastoma tumors expressed the caspase 8l isoform, whereas caspase 8l was absent in 3 of 3 ganglioneuromas. Seven human neuroblastoma cell lines were surveyed. Two of the 5 cell lines that expressed caspase 8 also expressed the caspase 8l isoform and both were of a less differentiated neuronal phenotype. Over-expression of caspase 8l in cell lines afforded protection against TRAIL, but not against etoposide induced apoptosis. Conversely, blockade of Caspase 8l in cells that express this splice variant made them more sensitive to apoptosis induced cell death. We demonstrate the caspase 8l isoform is present in neuroblastoma and appears to be associated with undifferentiated cell lines and tumors. Furthermore, it suppresses caspase 8-dependent apoptosis.
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2DOI: 10.1007/s10495-005-3258-0
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languageeng
publisherNetherlands: Springer
subjectAlternative Splicing ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Base Sequence ; Caspase 8 - genetics ; Caspase 8 - metabolism ; Caspase Inhibitors ; Caspase-8 ; Cell death ; Cell Differentiation ; Cell Line, Tumor ; Cell lines ; Cell Survival - physiology ; Cloning, Molecular ; DNA Primers - genetics ; Etoposide ; Gene Expression ; Humans ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Neuroblastoma ; Neuroblastoma - enzymology ; Neuroblastoma - genetics ; Neuroblastoma - pathology ; Overexpression ; Phenotype ; Phenotypes ; Prognosis ; TNF-Related Apoptosis-Inducing Ligand - pharmacology ; TRAIL protein ; Transfection ; Tumors
ispartofApoptosis (London), 2006-01, Vol.11 (1), p.15-24
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descriptionCaspase 8 is a key apoptotic factor in the receptor/ligand apoptosis-signaling cascade. Absent caspase 8 expression is shown to correlate with poor prognosis in neuroblastoma. Paradoxically, the caspase 8 gene can produce as plice variant and novel inhibitor of itself-caspase 8l. The presence of caspase 8 alone in tumors may not necessarily portend a good prognosis. We sought to determine whether caspase 8l is present in neuroblastoma and whether over-expression of this protein could inhibit caspase 8-dependent apoptosis. Six of 6 histologically undifferentiated and 2 of 5 differentiated neuroblastoma tumors expressed the caspase 8l isoform, whereas caspase 8l was absent in 3 of 3 ganglioneuromas. Seven human neuroblastoma cell lines were surveyed. Two of the 5 cell lines that expressed caspase 8 also expressed the caspase 8l isoform and both were of a less differentiated neuronal phenotype. Over-expression of caspase 8l in cell lines afforded protection against TRAIL, but not against etoposide induced apoptosis. Conversely, blockade of Caspase 8l in cells that express this splice variant made them more sensitive to apoptosis induced cell death. We demonstrate the caspase 8l isoform is present in neuroblastoma and appears to be associated with undifferentiated cell lines and tumors. Furthermore, it suppresses caspase 8-dependent apoptosis.
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32Transfection
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titleCaspase 8L, a novel inhibitory isoform of caspase 8, is associated with undifferentiated neuroblastoma
authorMiller, M A ; Karacay, B ; Zhu, X ; O'Dorisio, M S ; Sandler, A D
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abstractCaspase 8 is a key apoptotic factor in the receptor/ligand apoptosis-signaling cascade. Absent caspase 8 expression is shown to correlate with poor prognosis in neuroblastoma. Paradoxically, the caspase 8 gene can produce as plice variant and novel inhibitor of itself-caspase 8l. The presence of caspase 8 alone in tumors may not necessarily portend a good prognosis. We sought to determine whether caspase 8l is present in neuroblastoma and whether over-expression of this protein could inhibit caspase 8-dependent apoptosis. Six of 6 histologically undifferentiated and 2 of 5 differentiated neuroblastoma tumors expressed the caspase 8l isoform, whereas caspase 8l was absent in 3 of 3 ganglioneuromas. Seven human neuroblastoma cell lines were surveyed. Two of the 5 cell lines that expressed caspase 8 also expressed the caspase 8l isoform and both were of a less differentiated neuronal phenotype. Over-expression of caspase 8l in cell lines afforded protection against TRAIL, but not against etoposide induced apoptosis. Conversely, blockade of Caspase 8l in cells that express this splice variant made them more sensitive to apoptosis induced cell death. We demonstrate the caspase 8l isoform is present in neuroblastoma and appears to be associated with undifferentiated cell lines and tumors. Furthermore, it suppresses caspase 8-dependent apoptosis.
copNetherlands
pubSpringer
pmid16374545
doi10.1007/s10495-005-3258-0