High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model.
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.
Wei
Qingxia
Q
Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, University Health Network, Toronto, Ontario, Canada.
Clarke
Laura
L
Scheidenhelm
Danielle K
DK
Qian
Baoping
B
Tong
Amanda
A
Sabha
Nesrin
N
Karim
Zia
Z
Bock
Nicholas A
NA
Reti
Robert
R
Swoboda
Rolf
R
Purev
Enkhtsetseg
E
Lavoie
Jean-Francois
JF
Bajenaru
M Livia
ML
Shannon
Patrick
P
Herlyn
Dorothee
D
Kaplan
David
D
Henkelman
R Mark
RM
Gutmann
David H
DH
Guha
Abhijit
A
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002712:Chlorides; D003287:Contrast Media; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C025340:manganese chloride