XIAP is not required for human tumor cell survival in the absence of an exogenous death signal

BMC Cancer

Research Article

John Sensintaffar¹  Jeffrey H Hager¹  Fiona L Scott²  Robert Peach² 

[1] Aragon Pharmaceuticals, 4215 Sorrento Valley Blvd., Suite 215, 92121, San Diego, CA, USA;Biology, Apoptos Inc, 10835 Road to the Cure, 92130, San Diego, CA, USA;

关键词: SAHA;    Human Tumor Cell Line;    siRNA Treated Cell;    Trail Mediate Apoptosis;    Proteasome Inhibitor Bortezomib;   

DOI  :  10.1186/1471-2407-10-11

 received in 2009-06-12, accepted in 2010-01-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe X-linked Inhibitor of Apoptosis (XIAP) has attracted much attention as a cancer drug target. It is the only member of the IAP family that can directly inhibit caspase activity in vitro, and it can regulate apoptosis and other biological processes through its C-terminal E3 ubiquitin ligase RING domain. However, there is controversy regarding XIAP's role in regulating tumor cell proliferation and survival under normal growth conditions in vitro.MethodsWe utilized siRNA to systematically knock down XIAP in ten human tumor cell lines and then monitored both XIAP protein levels and cell viability over time. To examine the role of XIAP in the intrinsic versus extrinsic cell death pathways, we compared the viability of XIAP depleted cells treated either with a variety of mechanistically distinct, intrinsic pathway inducing agents, or the canonical inducer of the extrinsic pathway, TNF-related apoptosis-inducing ligand (TRAIL).ResultsXIAP knockdown had no effect on the viability of six cell lines, whereas the effect in the other four was modest and transient. XIAP knockdown only sensitized tumor cells to TRAIL and not the mitochondrial pathway inducing agents.ConclusionsThese data indicate that XIAP has a more central role in regulating death receptor mediated apoptosis than it does the intrinsic pathway mediated cell death.

【 授权许可】

Unknown   
© Sensintaffar et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.