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

Abstract

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.

• Authors: Andrea Muscat, Christine Hawkins, David M Ashley
• Journal: Cancer (Cancer) Vol. 107 Issue 4 Pg. 824-31 (Aug 15 2006) ISSN: 0008-543X [Print] United States
• PMID: 16886176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• STAT1 Transcription Factor
• CASP8 protein, human
• Caspase 8
• Caspases

Topics

• Caspase 8
• Caspases (metabolism)
• Cell Line, Tumor
• Child
• Child, Preschool
• DNA Methylation
• DNA, Neoplasm (genetics)
• Female
• Humans
• Immunoblotting
• Infant
• Infant, Newborn
• Male
• Neoplasm Staging
• Neuroblastoma (metabolism, pathology)
• Promoter Regions, Genetic
• STAT1 Transcription Factor (metabolism)