Oligodendrogliomas Result from the Expression of an Activated Mutant Epidermal Growth Factor Receptor in a RAS Transgenic Mouse Astrocytoma Model

摘要: A significant proportion of human malignant gliomas exhibit amplification, overexpression, or mutations the epidermal growth factor receptor (EGFR). To define functional role(s) EGFR in pathogenesis gliomas, we established transgenic mice that express both wild-type (wt) and mutant (EGFRvIII) molecules using glial fibrillary acidic protein (GFAP) promoter. Both GFAP-EGFR(wt) GFAP-EGFRvIII demonstrated increased numbers astrocytes compared with control littermates, however, developed normally without formation gliomas. determine whether overexpression could modify tumor phenotype our previously reported GFAP-V(12)Ha-ras mouse astrocytoma model, expressing activated RAS were developed. GFAP-V(12)Ha-ras;GFAP-EGFRvIII, but not GFAP-V(12)Ha-ras;GFAP-EGFR(wt) double mice, had decreased survival fifty percent dead at 2-4 weeks from 12-16 for mice. Furthermore, GFAP-V(12)Ha-ras;GFAP-EGFRvIII oligodendrogliomas mixed oligoastrocytoma tumors, instead astrocytomas observed In addition to yielding a spontaneous model infiltrating oligodendroglioma, this study demonstrates astrocyte-specific expression EGFRvIII alone is insufficient gliomagenesis rather contributes glioma progression context existing predisposing genetic changes.