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

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 15; pp. 7429 - 7437
• Main Authors: QINGXIA WEI, CLARKE, Laura, PUREV, Enkhtsetseg, LAVOIE, Jean-Francois, BAJENARU, M. Livia, SHANNON, Patrick, HERLYN, Dorothee, KAPLAN, David, HENKELMAN, R. Mark, GUTMANN, David H, GUHA, Abhijit, SCHEIDENHELM, Danielle K, BAOPING QIAN, TONG, Amanda, SABHA, Nesrin, KARIM, Zia, BOCK, Nicholas A, RETI, Robert, SWOBODA, Rolf
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-08-2006
• Subjects: Animals; Biological and medical sciences; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Chlorides; Contrast Media; Disease Models, Animal; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Silencing; Glioma - enzymology; Glioma - genetics; Glioma - pathology; Magnetic Resonance Imaging; Manganese Compounds; Medical sciences; Mice; Mice, Inbred ICR; Mice, Transgenic; Neurology; PTEN Phosphohydrolase - deficiency; PTEN Phosphohydrolase - genetics; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Tumors of the nervous system. Phacomatoses; Animal model; Nervous system diseases; Rodentia; Transgenic animal; Gene expression; Epidermal growth factor receptor; High grade; Vertebrata; Growth factor receptor; Mammalia; Postnatal; Glioma; Mouse; Central nervous system disease; Tumor; PTEN Gene; Mutation; Tumor suppressor gene; High malignancy
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-06-0712

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.