Interferon-γ Induces Caspase-8 in Neuroblastomas Without Affecting Methylation of Caspase-8 Promoter

Sunghoon Kim, Junghee Kang, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: The expression of caspase-8, a cysteine protease that is crucial for the apoptotic cascade, is absent in a high percentage of neuroblastomas, the most frequent extracranial solid tumor of infants and children. Resistance of neuroblastomas to death-receptor (eg, tumor necrosis factor alpha (TNF-α) receptor)-mediated apoptosis is thought to be caused by loss of caspase-8 expression. Gene silencing by hypermethylation of caspase-8 promoter has been proposed for the loss of caspase-8 expression in neuroblastoma cells. Methods: To further evaluate the role of caspase-8 in neuroblastoma, we assessed the induction of caspase-8 expression in neuroblastoma cells by treating the cells with a physiologic agent such as interferon-γ. Results: The authors found that interferon-γ induces caspase-8 expression in neuroblastoma cells irrespective of the gene silenced by hypermethylation of caspase-8 promoter. The authors show that interferon-γ also regulates other apoptosis related gene expression. Moreover, they show that interferon-γ treatment in combination with TNF-α decreases neuroblastoma cell proliferation. Conclusions: Interferon-γ induces procaspase-8 expression in neuroblastoma cells, and this induction is not dependent on demethylation of the caspase-8 promoter. Therapies aimed at inducing caspase-8 expression by adjunctive treatment, such as interferon-γ, may increase the effectiveness of current chemotherapeutic regimens.

Original languageEnglish (US)
Pages (from-to)509-515
Number of pages7
JournalJournal of Pediatric Surgery
Volume39
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Caspase 8
Neuroblastoma
Interferons
Methylation
Tumor Necrosis Factor-alpha
Apoptosis
Death Domain Receptors
Cysteine Proteases
Tumor Necrosis Factor Receptors
Gene Silencing
Therapeutics
Cell Proliferation
Gene Expression

Keywords

  • Caspase-8
  • Interferon-γ
  • Methylation-specific polymerase chain reaction
  • Neuroblastoma
  • Tumor necrosis factor alpha

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Interferon-γ Induces Caspase-8 in Neuroblastomas Without Affecting Methylation of Caspase-8 Promoter. / Kim, Sunghoon; Kang, Junghee; Evers, B. Mark; Chung, Dai H.

In: Journal of Pediatric Surgery, Vol. 39, No. 4, 04.2004, p. 509-515.

Research output: Contribution to journalArticle

@article{8074d30c938349d688b42de23c0edd4a,
title = "Interferon-γ Induces Caspase-8 in Neuroblastomas Without Affecting Methylation of Caspase-8 Promoter",
abstract = "Background: The expression of caspase-8, a cysteine protease that is crucial for the apoptotic cascade, is absent in a high percentage of neuroblastomas, the most frequent extracranial solid tumor of infants and children. Resistance of neuroblastomas to death-receptor (eg, tumor necrosis factor alpha (TNF-α) receptor)-mediated apoptosis is thought to be caused by loss of caspase-8 expression. Gene silencing by hypermethylation of caspase-8 promoter has been proposed for the loss of caspase-8 expression in neuroblastoma cells. Methods: To further evaluate the role of caspase-8 in neuroblastoma, we assessed the induction of caspase-8 expression in neuroblastoma cells by treating the cells with a physiologic agent such as interferon-γ. Results: The authors found that interferon-γ induces caspase-8 expression in neuroblastoma cells irrespective of the gene silenced by hypermethylation of caspase-8 promoter. The authors show that interferon-γ also regulates other apoptosis related gene expression. Moreover, they show that interferon-γ treatment in combination with TNF-α decreases neuroblastoma cell proliferation. Conclusions: Interferon-γ induces procaspase-8 expression in neuroblastoma cells, and this induction is not dependent on demethylation of the caspase-8 promoter. Therapies aimed at inducing caspase-8 expression by adjunctive treatment, such as interferon-γ, may increase the effectiveness of current chemotherapeutic regimens.",
keywords = "Caspase-8, Interferon-γ, Methylation-specific polymerase chain reaction, Neuroblastoma, Tumor necrosis factor alpha",
author = "Sunghoon Kim and Junghee Kang and Evers, {B. Mark} and Chung, {Dai H.}",
year = "2004",
month = "4",
doi = "10.1016/j.jpedsurg.2003.12.009",
language = "English (US)",
volume = "39",
pages = "509--515",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Interferon-γ Induces Caspase-8 in Neuroblastomas Without Affecting Methylation of Caspase-8 Promoter

AU - Kim, Sunghoon

AU - Kang, Junghee

AU - Evers, B. Mark

AU - Chung, Dai H.

PY - 2004/4

Y1 - 2004/4

N2 - Background: The expression of caspase-8, a cysteine protease that is crucial for the apoptotic cascade, is absent in a high percentage of neuroblastomas, the most frequent extracranial solid tumor of infants and children. Resistance of neuroblastomas to death-receptor (eg, tumor necrosis factor alpha (TNF-α) receptor)-mediated apoptosis is thought to be caused by loss of caspase-8 expression. Gene silencing by hypermethylation of caspase-8 promoter has been proposed for the loss of caspase-8 expression in neuroblastoma cells. Methods: To further evaluate the role of caspase-8 in neuroblastoma, we assessed the induction of caspase-8 expression in neuroblastoma cells by treating the cells with a physiologic agent such as interferon-γ. Results: The authors found that interferon-γ induces caspase-8 expression in neuroblastoma cells irrespective of the gene silenced by hypermethylation of caspase-8 promoter. The authors show that interferon-γ also regulates other apoptosis related gene expression. Moreover, they show that interferon-γ treatment in combination with TNF-α decreases neuroblastoma cell proliferation. Conclusions: Interferon-γ induces procaspase-8 expression in neuroblastoma cells, and this induction is not dependent on demethylation of the caspase-8 promoter. Therapies aimed at inducing caspase-8 expression by adjunctive treatment, such as interferon-γ, may increase the effectiveness of current chemotherapeutic regimens.

AB - Background: The expression of caspase-8, a cysteine protease that is crucial for the apoptotic cascade, is absent in a high percentage of neuroblastomas, the most frequent extracranial solid tumor of infants and children. Resistance of neuroblastomas to death-receptor (eg, tumor necrosis factor alpha (TNF-α) receptor)-mediated apoptosis is thought to be caused by loss of caspase-8 expression. Gene silencing by hypermethylation of caspase-8 promoter has been proposed for the loss of caspase-8 expression in neuroblastoma cells. Methods: To further evaluate the role of caspase-8 in neuroblastoma, we assessed the induction of caspase-8 expression in neuroblastoma cells by treating the cells with a physiologic agent such as interferon-γ. Results: The authors found that interferon-γ induces caspase-8 expression in neuroblastoma cells irrespective of the gene silenced by hypermethylation of caspase-8 promoter. The authors show that interferon-γ also regulates other apoptosis related gene expression. Moreover, they show that interferon-γ treatment in combination with TNF-α decreases neuroblastoma cell proliferation. Conclusions: Interferon-γ induces procaspase-8 expression in neuroblastoma cells, and this induction is not dependent on demethylation of the caspase-8 promoter. Therapies aimed at inducing caspase-8 expression by adjunctive treatment, such as interferon-γ, may increase the effectiveness of current chemotherapeutic regimens.

KW - Caspase-8

KW - Interferon-γ

KW - Methylation-specific polymerase chain reaction

KW - Neuroblastoma

KW - Tumor necrosis factor alpha

UR - http://www.scopus.com/inward/record.url?scp=8544250516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8544250516&partnerID=8YFLogxK

U2 - 10.1016/j.jpedsurg.2003.12.009

DO - 10.1016/j.jpedsurg.2003.12.009

M3 - Article

C2 - 15065018

AN - SCOPUS:8544250516

VL - 39

SP - 509

EP - 515

JO - Journal of Pediatric Surgery

JF - Journal of Pediatric Surgery

SN - 0022-3468

IS - 4

ER -