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Open Access Research

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

Franziska Wachter1, Michaela Grunert1, Cristina Blaj1, David M Weinstock2, Irmela Jeremias13 and Harald Ehrhardt14*

Author Affiliations

1 Helmholtz Zentrum München, German Research Center for Environmental Health, Marchioninistrasse 25, Munich, D-81377, Germany

2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

3 Department of Oncology / Hematology, Dr. von Haunersches Kinderspital, Lindwurmstr 4, München, 80337, Germany

4 Division of Neonatology, University Children’s Hospital, Perinatal Center, Ludwig-Maximilians-University Munich, Marchioninistr 15, Munich, 81377, Germany

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Cell Communication and Signaling 2013, 11:27  doi:10.1186/1478-811X-11-27

Published: 17 April 2013

Abstract

Background

The 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.

Results

We 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.

Conclusions

In 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.

Keywords:
p53; Mutant p53; Extrinsic; Intrinsic; TRAIL; Doxorubicin; Apoptosis