gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Raf expression by human astrocytic tumors

Raf-Expression durch humane astrozytäre Tumore

Meeting Abstract

  • corresponding author C. Hagemann - Universität Würzburg, Neurochirurgische Universitätsklinik, Tumorbiologisches Labor, Würzburg
  • J. Stojic - Universität Würzburg, Neurochirurgische Universitätsklinik, Tumorbiologisches Labor, Würzburg
  • J. Gloger - Universität Würzburg, Neurochirurgische Universitätsklinik, Tumorbiologisches Labor, Würzburg
  • C. Meyer - Universität des Saarlandes, Institut für Pharmazeutische Biologie, Saarbrücken
  • K. Roosen - Universität Würzburg, Neurochirurgische Universitätsklinik, Tumorbiologisches Labor, Würzburg
  • G. H. Vince - Universität Würzburg, Neurochirurgische Universitätsklinik, Tumorbiologisches Labor, Würzburg

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocDO.02.03

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc013.shtml

Veröffentlicht: 11. April 2007

© 2007 Hagemann et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Glioblastomas (GBM) are the most prevalent malignant brain tumors in adults. They are characterized by an aggressive local growth pattern and a marked degree of invasiveness, leading to poor prognosis. On genetic level, astrocytic tumors show a high degree of chromosomal instability and aneuploidy. Especially monosomy of chromosome 10 and trisomy of chormosome 7 is observed and often one of the sex chromosomes is lost. It is suggested that the genetic instability is the reason for the loss of tumorsuppressor genes and the overexpression of oncogenes. Known oncogenes are e.g. members of the Raf serine/threonine kinase family. However, the role of Raf proteins during development of astrocytic tumors has only rarely been addressed in the literature.

Methods: The expression pattern of the three Raf-isoforms was analysed in an extensive panel of three normal brain samples, 15 astrocytomas WHO grade 2 and 15 GBM by Southern-blotting, semiquantitative RT-PCR, Western-blotting and sequencing.

Results: Raf proteins are key components of the mitogenic signalling cascade. Three members are known: A-Raf, B-Raf and c-Raf-1. The B-raf gene maps to chromosome 7 and A-raf is localized on the X-chromosome. It has been shown that B-Raf and c-Raf-1 contain activating mutations in a high percentage of malignant melanomas and colon carcinomas. In contrast, a role for A-Raf during tumorigenesis has not been detected so far. Our analysis showed that activating Raf mutations are rare in GBM. No mutations were found in the A-Raf gene and only 2% of the tumors contained activating B-Raf mutations. However, all three Raf proteins were overexpressed in astrocytic tumors. Especially A-Raf expression in GBM was negatively correlated with the patients survival. Functional assays using transient overexpression and siRNA mediated knock-down of A-Raf in cell culture did not reveal any influence of A-Raf on proliferation or migration of the cells. There are hints for an involvement of A-Raf in the regulation of the tumor cell's metabolism.

Conclusions: Raf proteins are clearly overexpressed in GBM and play a role during progression of these tumors. Therefore, the Raf isoforms are possible candidates for small molecule therapies.