HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

An activated mutant BRAF kinase domain is sufficient to induce pilocytic astrocytoma in mice.

Abstract
Pilocytic astrocytoma (PA) is the most common type of primary brain tumor in children and the second most frequent cancer in childhood. Children with incompletely resected PA represent a clinically challenging patient cohort for whom conventional adjuvant therapies are only moderately effective. This has produced high clinical demand for testing of new molecularly targeted treatments. However, the development of new therapeutics for PA has been hampered by the lack of an adequate in vivo tumor model. Recent studies have identified activation of MAPK signaling, mainly by oncogenic BRAF activation, as a hallmark genetic event in the pathogenesis of human PA. Using in vivo retroviral somatic gene transfer into mouse neural progenitor cells, we have shown here that ectopic expression of the activated BRAF kinase domain is sufficient to induce PA in mice. Further in vitro analyses demonstrated that overexpression of activated BRAF led to increased proliferation of primary mouse astrocytes that could be inhibited by treatment with the kinase inhibitor sorafenib. Our in vivo model for PA shows that the activated BRAF kinase domain is sufficient to induce PA and highlights its role as a potential therapeutic target.
AuthorsJan Gronych, Andrey Korshunov, Josephine Bageritz, Till Milde, Manfred Jugold, Dolores Hambardzumyan, Marc Remke, Christian Hartmann, Hendrik Witt, David T W Jones, Olaf Witt, Sabine Heiland, Martin Bendszus, Eric C Holland, Stefan Pfister, Peter Lichter
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 121 Issue 4 Pg. 1344-8 (Apr 2011) ISSN: 1558-8238 [Electronic] United States
PMID21403401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA Primers
  • Braf protein, mouse
  • Proto-Oncogene Proteins B-raf
Topics
  • Animals
  • Animals, Newborn
  • Astrocytoma (enzymology, etiology, genetics, pathology)
  • Base Sequence
  • Brain Neoplasms (enzymology, etiology, genetics, pathology)
  • DNA Primers (genetics)
  • Disease Models, Animal
  • Enzyme Activation
  • Gene Transfer Techniques
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Mutation
  • Oncogenes
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins B-raf (chemistry, genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: