Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN

Tal Teitz, Tie Wei, Marcus B. Valentine, Elio F. Vanin, Jose Grenet, Virginia A. Valentine, Frederick G. Behm, A. Thomas Look, Jill M. Lahti, Vincent J. Kidd

Research output: Contribution to journalArticlepeer-review

672 Scopus citations

Abstract

Caspase 8 is a cysteine protease regulated in both a death-receptor- dependent and -independent manner during apoptosis. Here, we report that the gene for caspase 8 is frequently inactivated in neuroblastoma, a childhood tumor of the peripheral nervous system. The gene is silenced through DNA methylation as well as through gene deletion. Complete inactivation of CASP8 occurred almost exclusively in neuroblastomas with amplification of the oncogene MYCN. Caspase 8-null neuroblastoma cells were resistant to death receptor- and doxorubicin-mediated apoptosis, deficits that were corrected by programmed expression of the enzyme. Thus, caspase 8 acts as a tumor suppressor in neuroblastomas with amplification of MYCN.

Original languageEnglish (US)
Pages (from-to)529-535
Number of pages7
JournalNature Medicine
Volume6
Issue number5
DOIs
StatePublished - May 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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