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

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.

• Authors: T J Zuzak, D F Steinhoff, L N Sutton, P C Phillips, A Eggert, M A Grotzer
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 38 Issue 1 Pg. 83-91 (Jan 2002) ISSN: 0959-8049 [Print] England
• PMID: 11750844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• CASP8 and FADD-Like Apoptosis Regulating Protein
• CFLAR protein, human
• Carrier Proteins
• FADD protein, human
• Fas-Associated Death Domain Protein
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• Neoplasm Proteins
• RNA, Messenger
• RNA, Neoplasm
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor
• TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10B protein, human
• TNFSF10 protein, human
• Tumor Necrosis Factor-alpha
• CASP3 protein, human
• CASP8 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases

Topics

• Adaptor Proteins, Signal Transducing
• Adolescent
• Apoptosis Regulatory Proteins
• Brain Neoplasms (enzymology)
• CASP8 and FADD-Like Apoptosis Regulating Protein
• Carrier Proteins (metabolism)
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases (metabolism)
• Child
• Child, Preschool
• DNA Methylation
• Fas-Associated Death Domain Protein
• Female
• Humans
• Intracellular Signaling Peptides and Proteins
• Male
• Medulloblastoma (enzymology)
• Membrane Glycoproteins (metabolism)
• Neoplasm Proteins (metabolism)
• Neuroectodermal Tumors, Primitive (metabolism)
• RNA, Messenger (metabolism)
• RNA, Neoplasm
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• TNF-Related Apoptosis-Inducing Ligand
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (metabolism)