RAF expression in human astrocytic tumors

  • Authors:
    • Carsten Hagemann
    • Jens Gloger
    • Jelena Anacker
    • Harun M. Said
    • Stefanie Gerngras
    • Siglinde Kühnel
    • Christoph Meyer
    • Ulf Rüdiger Rapp
    • Ulrike Kämmerer
    • Dirk Vordermark
    • Michael Flentje
    • Klaus Roosen
    • Giles Hamilton Vince
  • View Affiliations

  • Published online on: January 1, 2009     https://doi.org/10.3892/ijmm_00000097
  • Pages: 17-31
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

RAF proteins are well known oncoproteins. The B-RAF has been shown to be activated by mutations in a multitude of human cancers. Alterations of C-RAF expression are discussed to play a role in lung cancer. Only for A-RAF no link to tumorigenesis has been published so far. Malignant gliomas are the most prevalent primary brain tumors of adults. They are highly invasive and very difficult to treat, despite of surgery, γ-irradiation and chemotherapy. Although a role of the mitogenic Ras-RAF-MEK-ERK signalling cascade in brain tumor development is well established, there are only few reports available addressing alterations in RAF sequence or protein expression and function in human gliomas. We analysed the mutational status of A-RAF and B-RAF in human glioblastomas (GBM) by sequencing. Then we checked for RAF gene amplification by dot blot hybridization and examined RAF mRNA and protein expression patterns in human astrocytic gliomas of WHO grade II (LGA) and IV (GBM) by semiquantitative RT-PCR and Western blotting, respectively. The results were correlated with patients prognosis. Finally, we performed functional assays to address a putative function of A-RAF in glioma cell proliferation and migration. We showed that RAF mutations are a rare event in glioblastoma multiforme. A-raf gene amplification was more often detected and overexpression of all three RAF proteins on mRNA and protein level was regularly found in human malignant gliomas. Whereas A-RAF and C-RAF expression was negatively correlated with the patients prognosis, B-RAF expression had a positive effect. Since neither A-RAF, nor C-RAF expression had any influence on proliferation and migration of GBM cells, putative functions of C-RAF in angiogenesis and of A-RAF in regulation of metabolism are discussed. Our data indicate that RAF proteins might be valuable targets for small molecule therapies. However, initially specific functions of RAF during tumorigenesis have to be elucidated.

Related Articles

Journal Cover

January 2009
Volume 23 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Hagemann C, Gloger J, Anacker J, Said HM, Gerngras S, Kühnel S, Meyer C, Rapp UR, Kämmerer U, Vordermark D, Vordermark D, et al: RAF expression in human astrocytic tumors. Int J Mol Med 23: 17-31, 2009
APA
Hagemann, C., Gloger, J., Anacker, J., Said, H.M., Gerngras, S., Kühnel, S. ... Vince, G.H. (2009). RAF expression in human astrocytic tumors. International Journal of Molecular Medicine, 23, 17-31. https://doi.org/10.3892/ijmm_00000097
MLA
Hagemann, C., Gloger, J., Anacker, J., Said, H. M., Gerngras, S., Kühnel, S., Meyer, C., Rapp, U. R., Kämmerer, U., Vordermark, D., Flentje, M., Roosen, K., Vince, G. H."RAF expression in human astrocytic tumors". International Journal of Molecular Medicine 23.1 (2009): 17-31.
Chicago
Hagemann, C., Gloger, J., Anacker, J., Said, H. M., Gerngras, S., Kühnel, S., Meyer, C., Rapp, U. R., Kämmerer, U., Vordermark, D., Flentje, M., Roosen, K., Vince, G. H."RAF expression in human astrocytic tumors". International Journal of Molecular Medicine 23, no. 1 (2009): 17-31. https://doi.org/10.3892/ijmm_00000097