High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model.
High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model.
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DOI：
10.1158/0008-5472.can-06-0712
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发表时间：
2006-08
期刊：
影响因子：
11.2
通讯作者：
Qingxia Wei;Laura Clarke;Danielle K. Scheidenhelm;Baoping Qian;A. Tong;N. Sabha;Zia Karim;N. Bock;R. Reti;R. Swoboda;E. Purev;Jean-François Lavoie;M. Bajenaru;P. Shannon;D. Herlyn;David L. Kaplan;R. Henkelman;D. Gutmann;A. Guha
中科院分区：
文献类型：
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作者：
Qingxia Wei;Laura Clarke;Danielle K. Scheidenhelm;Baoping Qian;A. Tong;N. Sabha;Zia Karim;N. Bock;R. Reti;R. Swoboda;E. Purev;Jean-François Lavoie;M. Bajenaru;P. Shannon;D. Herlyn;David L. Kaplan;R. Henkelman;D. Gutmann;A. Guha
高级别胶质瘤是毁灭性的脑肿瘤，平均生存期<50周。在这些肿瘤中观察到的两种最常见的遗传变化是表皮生长因子受体（EGFR）vIII的过表达/突变和PTEN/MMAC 1表达的丧失。为了确定体细胞获得的EGFRvIII表达或Pten丢失是否加速了高级别胶质瘤的发展，我们使用了先前表征的RasB 8胶质瘤易感小鼠品系，其中这些特定的遗传变化在4周龄时被局部引入。我们发现RasB 8小鼠的出生后EGFRvIII表达和Pten失活都增强了高级别胶质瘤的发展。此外，我们观察到Pten和EGFR过表达的一致损失，在几乎所有的高级别胶质瘤诱导的EGFRvIII的引入或Pten失活。这种新型的高级别胶质瘤临床前模型将有助于评估针对EGFR表达或Pten丢失特异性失调的途径的脑肿瘤疗法。
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.