Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumour/medulloblastoma

T. J. Zuzak, D. F. Steinhoff, L. N. Sutton, P. C. Phillips, A. Eggert, M. A. Grotzer

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Upon binding of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), the agonistic TRAIL receptors DR4 and DR5 activate caspase-8 leading to apoptosis. In primitive neuroectodermal brain tumour (PNET) cell lines, TRAIL-induced apoptosis was recently shown to correlate with caspase-8 mRNA expression (Grotzer MA, Eggert A, Zuzak TJ, et al. Oncogene 2000, 19, 4604-4610). In this study, we analysed the expression of the TRAIL death pathway in 27 primary PNET/medulloblastoma. As shown by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), all PNET/medulloblastoma evaluated expressed DR5, the adapter protein FADD and caspase-3, but only 48% expressed caspase-8. The mRNA expression of caspase-8 was significantly lower in primary PNET/medulloblastoma compared with normal brain samples. PCR revealed >75% methylation of the caspase-8 promoter region in three of seven PNET cell lines and in 55% of the primary PNET/medulloblastoma evaluated. In the PNET cell lines, the methylation status correlated with the caspase-8 mRNA expression. We conclude that loss of caspase-8 gene expression is common in PNET/medulloblastoma suggesting that suppression of death receptor induced apoptosis may play an important role in the pathogenesis of this common childhood brain tumour.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalEuropean Journal of Cancer
Volume38
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Brain tumour
  • Caspase-8
  • Medulloblastoma
  • Pathogenesis
  • Primitive neuroectodermal tumour
  • TRAIL (Apo2L)

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