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Cancer Research 67, 2396, March 15, 2007. doi: 10.1158/0008-5472.CAN-06-2425
© 2007 American Association for Cancer Research
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Priority Reports

Mutant p53 Enhances Nuclear Factor {kappa}B Activation by Tumor Necrosis Factor {alpha} in Cancer Cells

Lilach Weisz1, Alexander Damalas1,2,5, Michalis Liontos5, Panagiotis Karakaidos5, Giulia Fontemaggi2,3, Revital Maor-Aloni1, Marina Kalis1, Massimo Levrero2,3,4, Sabrina Strano2, Vassilis G. Gorgoulis5, Varda Rotter1, Giovanni Blandino2,3 and Moshe Oren1

1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; 2 Department of Experimental Oncology, Regina Elena Cancer Institute, 3 Rome Oncogenomic Center, Via delle Messi d'oro and 4 Fondazione Andrea Cesalpino, University La Sapienza, Rome, Italy; and 5 Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Greece

Requests for reprints: Moshe Oren, Molecular Cell Biology, Weizmann Institute, Rehovot 76100, Israel. Phone: 972-8-9342358; Fax: 972-8-9346004; E-mail: moshe.oren{at}weizmann.ac.il.

Mutations in the p53 tumor suppressor are very frequent in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 proteins, which may exert a cancer-promoting gain of function. We now report that cancer-associated mutant p53 can augment the induction of nuclear factor {kappa}B (NF{kappa}B) transcriptional activity in response to the cytokine tumor necrosis factor {alpha} (TNF{alpha}). Conversely, down-regulation of endogenous mutant p53 sensitizes cancer cells to the apoptotic effects of TNF{alpha}. Analysis of human head and neck tumors and lung tumors reveals a close correlation between the presence of abundant mutant p53 proteins and the constitutive activation of NF{kappa}B. Together, these findings suggest that p53 mutations may promote cancer progression by augmenting NF{kappa}B activation in the context of chronic inflammation. [Cancer Res 2007;67(6):2396–401]




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Copyright © 2007 by the American Association for Cancer Research.