gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Functional interaction between tumor suppressor p53 and proto-oncogene Ets-1 determines the invasive potential of glial tumors

Die Interaktion von Tumorsuppressor p53 und Proto-Onkogen Ets-1 bestimmt das invasive Potential glialer Tumore

Meeting Abstract

  • E. Kim - Neurochirurgische Universitätsklinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • S, Schlaffer - Neurochirurgische Universitätsklinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • E. Pawlak - Neurochirurgische Universitätsklinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • W. Deppert - Heinrich-Pette Institut, Universität Hamburg, Hamburg
  • H. Arnold - Neurochirurgische Universitätsklinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
  • corresponding author Alf Giese - Neurochirurgische Universitätsklinik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 04.39

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2004/04dgnc0322.shtml

Published: April 23, 2004

© 2004 Kim et al.
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Outline

Text

Objective

The proto-oncogenic factor Ets-1 is directly associated with progression and invasion and is frequently overexpressed in gliomas but not in normal glial cells. While the importance of Ets-1 in glioma invasion has already been established, the mechanisms leading to deregulated expression of Ets-1 remain poorly understood. We have recently discovered that the transcriptional activity of Ets-1 is under the control of tumor suppressor p53, which associates physically with the Ets-1 protein and abrogates Ets-1 dependent expression of anti-apoptotic and invasion genes.

Methods

Steady-state levels of the Ets-1 protein were examined in glioma cells lines by western blot. p53´s transcriptional activity was induced in lines expressing wild type p53 by γ-radiation. Expression pattern of known p53 target genes MDM2 and P21 were used to determine p53´s transcriptional activity.

Results

The negative control of Ets-1 activities by p53 extends beyond physical interaction between the two proteins. Not only the Ets-1 activity, but also expression of the Ets-1 protein, is under a negative control by p53. Inhibition of Ets-1 expression requires transcriptionally active p53 protein and is no longer affected by p53 mutants. Treatment of glioma cells with γ-radiation in regimens similar to those used in clinical practice induces ets-1 depending on the functional status of the p53 protein.

Conclusions

Our findings identify Ets-1 as a novel target gene of p53. Based on our findings we propose that aberrant interaction between p53 and Ets-1 determines the high invasive potential and resistance to apoptosis in gliomas. Furthermore, we propose that in cells with impaired function of tumor suppressor p53, γ-radiation leads to induction of Ets-1 and subsequent induction of anti-apoptotic and invasion-associated genes.