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Caspase‐8 levels correlate with the expression of signal transducer and activator of transcription 1 in high‐grade but not lower grade neuroblastoma
Author(s) -
Muscat Andrea,
Hawkins Christine,
Ashley David M.
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22052
Subject(s) - methylation , stat protein , dna methylation , promoter , transcription (linguistics) , gene silencing , biology , cancer research , microbiology and biotechnology , caspase 3 , stat , exon , transcription factor , gene , gene expression , stat3 , apoptosis , genetics , programmed cell death , linguistics , philosophy
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 γ‐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. Cancer 2006. © 2006 American Cancer Society.