High-Grade Glioma Formation Results from Postnatal Pten Loss or Mutant Epidermal Growth Factor Receptor Expression in a Transgenic Mouse Glioma Model Academic Article uri icon

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abstract

  • High-grade gliomas are devastating brain tumors associated with a mean survival of <50 weeks. Two of the most common genetic changes observed in these tumors are overexpression/mutation of the epidermal growth factor receptor (EGFR) vIII and loss of PTEN/MMAC1 expression. To determine whether somatically acquired EGFRvIII expression or Pten loss accelerates high-grade glioma development, we used a previously characterized RasB8 glioma-prone mouse strain, in which these specific genetic changes were focally introduced at 4 weeks of age. We show that both postnatal EGFRvIII expression and Pten inactivation in RasB8 mice potentiate high-grade glioma development. Moreover, we observe a concordant loss of Pten and EGFR overexpression in nearly all high-grade gliomas induced by either EGFRvIII introduction or Pten inactivation. This novel preclinical model of high-grade glioma will be useful in evaluating brain tumor therapies targeted to the pathways specifically dysregulated by EGFR expression or Pten loss.

authors

  • Wei, Qingxia
  • Clarke, Laura
  • Scheidenhelm, Danielle K
  • Qian, Baoping
  • Tong, Amanda
  • Sabha, Nesrin
  • Karim, Zia
  • Bock, Nicholas
  • Reti, Robert
  • Swoboda, Rolf
  • Purev, Enkhtsetseg
  • Lavoie, Jean-Francois
  • Bajenaru, M Livia
  • Shannon, Patrick
  • Herlyn, Dorothee
  • Kaplan, David
  • Henkelman, R Mark
  • Gutmann, David H
  • Guha, Abhijit

publication date

  • August 1, 2006

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