Nature Medicine
6, 529 - 535 (2000)
doi:10.1038/75007
Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas
with amplification of MYCNTal Teitz1, Tie Wei1, Marcus B. Valentine1, 3, Elio F. Vanin2, Jose Grenet1, Virginia A. Valentine1, 3, Frederick G. Behm4, A. Thomas Look3, 5, Jill M. Lahti1
& Vincent J. Kidd11
Department of Tumor Cell Biology, St. Jude Children's
Research Hospital, 332 N. Lauderdale, Memphis
, Tennessee, 38101 USA
2
Department of Experimental Hematology, St. Jude Children's
Research Hospital, 332 N. Lauderdale, Memphis
, Tennessee, 38101 USA
3
Department of Experimental Oncology, St. Jude Children's
Research Hospital, 332 N. Lauderdale, Memphis
, Tennessee, 38101 USA
4
Department of Pathology, St. Jude Children's Research
Hospital, 332 N. Lauderdale, Memphis,
Tennessee, 38101 USA
5
A.T.L. present address: Department of Pediatric Oncology,
Mayer Building-630, Dana-Farber Cancer Institute, 44 Binney
Street, Boston, Massachussetts 02115
Correspondence should be addressed to Vincent J. Kidd vincent.kidd@stjude.orgCaspase 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.
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