Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling

Cell Communication and Signaling

Research

David M Weinstock¹  Michaela Grunert²  Franziska Wachter²  Cristina Blaj²  Irmela Jeremias³  Harald Ehrhardt⁴ 

[1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA;German Research Center for Environmental Health, Helmholtz Zentrum München, Marchioninistrasse 25, D-81377, Munich, Germany;German Research Center for Environmental Health, Helmholtz Zentrum München, Marchioninistrasse 25, D-81377, Munich, Germany;Department of Oncology / Hematology, Dr. von Haunersches Kinderspital, Lindwurmstr 4, 80337, München, Germany;German Research Center for Environmental Health, Helmholtz Zentrum München, Marchioninistrasse 25, D-81377, Munich, Germany;Division of Neonatology, University Children’s Hospital, Perinatal Center, Ludwig-Maximilians-University Munich, Marchioninistr 15, 81377, Munich, Germany;

关键词: p53;    Mutant p53;    Extrinsic;    Intrinsic;    TRAIL;    Doxorubicin;    Apoptosis;   

DOI  :  10.1186/1478-811X-11-27

 received in 2012-08-27, accepted in 2013-04-03,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling.ResultsWe reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity.ConclusionsIn summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.

【 授权许可】

Unknown   
© Wachter et al.; licensee BioMed Central Ltd. 2013. 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.