Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression
2000; Alan R. Liss, Inc.; Volume: 35; Issue: 6 Linguagem: Inglês
10.1002/1096-911x(20001201)35
ISSN1096-911X
AutoresAngelika Eggert, Michael Grotzer, Tycho Jan Zuzak, Barbara R. Wiewrodt, Naohiko Ikegaki, Garrett M. Brodeur,
Tópico(s)interferon and immune responses
ResumoMedical and Pediatric OncologyVolume 35, Issue 6 p. 603-607 Original Article Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression Angelika Eggert MD, Angelika Eggert MD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorMichael A. Grotzer MD, Michael A. Grotzer MD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorTycho J. Zuzak BS, Tycho J. Zuzak BS Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorBarbara R. Wiewrodt MD, Barbara R. Wiewrodt MD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorNaohiko Ikegaki PhD, Naohiko Ikegaki PhD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorGarrett M. Brodeur MD, Corresponding Author Garrett M. Brodeur MD [email protected] Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaThe Children's Hospital of Philadelphia, Division of Oncology, ARC Rm. 902-D, 3516 Civic Center Boulevard, Philadelphia, PA 19104Search for more papers by this author Angelika Eggert MD, Angelika Eggert MD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorMichael A. Grotzer MD, Michael A. Grotzer MD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorTycho J. Zuzak BS, Tycho J. Zuzak BS Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorBarbara R. Wiewrodt MD, Barbara R. Wiewrodt MD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorNaohiko Ikegaki PhD, Naohiko Ikegaki PhD Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaSearch for more papers by this authorGarrett M. Brodeur MD, Corresponding Author Garrett M. Brodeur MD [email protected] Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaThe Children's Hospital of Philadelphia, Division of Oncology, ARC Rm. 902-D, 3516 Civic Center Boulevard, Philadelphia, PA 19104Search for more papers by this author First published: 30 November 2000 https://doi.org/10.1002/1096-911X(20001201)35:6 3.0.CO;2-1Citations: 40AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Background Disruption of apoptotic pathways may be involved in tumor formation, regression, and treatment resistance of neuroblastoma (NB). TNF-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in cancer cell lines. Procedure In this study we analyzed the expression and function of TRAIL, its agonistic and antagonistic receptors, and important intracellular signaling elements in 18 NB cell lines. Results Semiquantitative RT-PCR revealed that TRAIL-R2 and TRAIL-R3 are the main TRAIL-receptors used by NB cells. Sensitivity to TRAIL-induced apoptosis did not correlate with mRNA expression of TRAIL receptors or cFLIP. Surprisingly, caspase-8 and caspase-10 mRNA was detected in only 5 of 18 NB cell lines. Interestingly, only these five NB cell lines were susceptible to TRAIL-induced apoptosis in a time- and dose-dependent manner. Conclusions Treatment with 5-aza-2′-deoxycytidine restored mRNA expression of caspase-8 and –10 and TRAIL sensitivity of resistant cell lines, suggesting that gene methylation is involved in caspase inactivation. Since many cytotoxic drugs induce caspase-dependent apoptosis, failure to express caspase-8 and/or caspase-10 might be an important mechanism of resistance to chemotherapy in NB. Med. Pediatr. Oncol. 35:603–607, 2000. © 2000 Wiley-Liss, Inc. Citing Literature Volume35, Issue6Special Issue: Advances in Neuroblastoma Research: 2000 Conference1 December 2000Pages 603-607 RelatedInformation
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