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27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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hGBP-1 inhibits UV induced nuclear accumulation of p53 tumor suppressor in human umbilical vein endothelial cells

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  • corresponding author presenting/speaker Kristina Weinländer - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg, Deutschland
  • Kristin Pogoda - Departement of Virus-induced Vasculopathy, Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
  • Mathias Thurau - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg
  • Werner Hohenberger - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg
  • Michael Stürzl - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO505

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk615.shtml

Published: March 20, 2006

© 2006 Weinländer et al.
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Outline

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The p53 tumor suppressor is a central stress response protein, activated by multiple endogenous and environmental insults. UV-irradiation of cells activates p53, causes accumulation of the tumor suppressor in the nucleus and induces apoptosis. Recently it was shown that growth-arrested cells are resistant to UV-light induced p53-dependent apoptosis. In previous studies we could show that the human guanylate binding protein-1 (hGBP-1) mediates the inhibition of cell proliferation induced by IFN-γ and double-stranded (ds) RNA in endothelial cells (EC). Here we wanted to analyse the effect of hGBP-1 on nuclear translocation of p53 after UV-irradiation in human umbilical vein endothelial cells (HUVEC).

We found that an upregulation of hGBP-1 expression in HUVEC induced by IFN-γ and dsRNA was accompanied by a reduced p53 intracellular protein concentration. In addition pretreatment of HUVEC with IFN-γ and dsRNA inhibited the UV induced nuclear accumulation of p53. In untreated EC nuclear translocation of p53 following UV-irradiation (100J/m2) was not disturbed. In a next step hGBP-1 was constitutively expressed in HUVEC by retroviral-mediated gene transfer. Of note, in these cells UV induced nuclear translocation of p53 was significantly (p < 0,001; chi square test) repressed even without pretreatment with IFN-γ or dsRNA. After UV-irradiation only 36% of hGBP-1 transduced cells showed nuclear accumulation of p53 as compared to 72 % of vector transduced control cells.

These results suggest that hGBP-1 may mediate the inhibition of UV induced p53 nuclear translocation in response to IFN-γ and dsRNA. This activity may effect p53 dependent apoptosis and could be of relevance in anti-angiogenic tumor therapy.