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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.

Publication ,  Journal Article
Muscat, A; Hawkins, C; Ashley, DM
Published in: Cancer
August 15, 2006

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.

Duke Scholars

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

August 15, 2006

Volume

107

Issue

4

Start / End Page

824 / 831

Location

United States

Related Subject Headings

  • STAT1 Transcription Factor
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neuroblastoma
  • Neoplasm Staging
  • Male
  • Infant, Newborn
  • Infant
  • Immunoblotting
  • Humans
 

Citation

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Muscat, A., Hawkins, C., & Ashley, D. M. (2006). Caspase-8 levels correlate with the expression of signal transducer and activator of transcription 1 in high-grade but not lower grade neuroblastoma. Cancer, 107(4), 824–831. https://doi.org/10.1002/cncr.22052
Muscat, Andrea, Christine Hawkins, and David M. Ashley. “Caspase-8 levels correlate with the expression of signal transducer and activator of transcription 1 in high-grade but not lower grade neuroblastoma.Cancer 107, no. 4 (August 15, 2006): 824–31. https://doi.org/10.1002/cncr.22052.
Muscat, Andrea, et al. “Caspase-8 levels correlate with the expression of signal transducer and activator of transcription 1 in high-grade but not lower grade neuroblastoma.Cancer, vol. 107, no. 4, Aug. 2006, pp. 824–31. Pubmed, doi:10.1002/cncr.22052.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

August 15, 2006

Volume

107

Issue

4

Start / End Page

824 / 831

Location

United States

Related Subject Headings

  • STAT1 Transcription Factor
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Neuroblastoma
  • Neoplasm Staging
  • Male
  • Infant, Newborn
  • Infant
  • Immunoblotting
  • Humans