Caspase-8 levels correlate with the expression of signal transducer and activator of transcription 1 in high-grade but not lower grade neuroblastoma.

Journal Article (Journal Article)

BACKGROUND: Previous studies in advanced-stage neuroblastoma (NB) have shown a link between the silencing of caspase-8 and methylation of a regulatory region at the boundary between caspase-8 exon 3 and intron 3. However, a number of recent studies from NB cell lines have shown that the transcriptional regulation of caspase-8 may reside with interferon gamma-sensitive promoters through the action of transcription factors, such as signal transducer and activator of transcription 1 (STAT-1). In this study, the authors tested the hypothesis that there is a correlation between caspase-8 and STAT-1 protein expression levels that may be linked to methylation of the regulatory elements of either of these genes. METHODS: Thirty clinical tumor samples of all stages, including 13 samples from patients with Stage 4 disease, were analyzed by quantitative immunoblotting for caspase-8 and STAT-1. The DNA methylation status of putative caspase-8 and STAT-1 regulatory elements were determined by bisulfite-modified sequencing analysis. RESULTS: A significant correlation was observed between caspase-8 and STAT-1 protein levels in Stage 4 NB samples but not in lower stage NB samples. Caspase-8 and STAT-1 protein levels varied widely across all stages of NB and did not correlate with methylation of these genes. CONCLUSIONS: A strong correlation was observed between STAT-1 levels and caspase-8 levels in clinical Stage 4 NB. This suggests that STAT-1 or similar transcription factors, and not methylation, may play a role in controlling caspase-8 levels in this illness. No evidence of such a correlation between caspase-8 and STAT-1 levels was observed in lower clinical stages, suggesting that mechanisms controlling caspase-8 expression in NB vary with clinical stage.

Full Text

Duke Authors

Cited Authors

  • Muscat, A; Hawkins, C; Ashley, DM

Published Date

  • August 15, 2006

Published In

Volume / Issue

  • 107 / 4

Start / End Page

  • 824 - 831

PubMed ID

  • 16886176

International Standard Serial Number (ISSN)

  • 0008-543X

Digital Object Identifier (DOI)

  • 10.1002/cncr.22052


  • eng

Conference Location

  • United States