High-grade glioma formation results from postnatal Pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model

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

Research output: Contribution to journalArticle

75 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7429-7437
Number of pages9
JournalCancer Research
Volume66
Issue number15
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wei, Q., Clarke, L., Scheidenhelm, D. K., Qian, B., Tong, A., Sabha, N., Karim, Z., Bock, N. A., Reti, R., Swoboda, R., Purev, E., Lavoie, J. F., Bajenaru, M. L., Shannon, P., Herlyn, D., Kaplan, D., Henkelman, R. M., Gutmann, D. H., & Guha, A. (2006). High-grade glioma formation results from postnatal Pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model. Cancer Research, 66(15), 7429-7437. https://doi.org/10.1158/0008-5472.CAN-06-0712