A Drosophila Model for EGFR-Ras and PI3K-Dependent Human Glioma

摘要: Gliomas, the most common malignant tumors of nervous system, frequently harbor mutations that activate epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling pathways. To investigate genetic basis this disease, we developed a glioma model in Drosophila. We found constitutive coactivation EGFR-Ras PI3K pathways Drosophila glia glial precursors gives rise to neoplastic, invasive cells create transplantable tumor-like growths, mimicking human glioma. Our represents robust organotypic cell-type-specific cancer which are created by signature genes thought be driving forces homologous cancer. Genetic analyses demonstrated EGFR initiate neoplastic transformation via combinatorial network composed primarily other commonly mutated or activated glioma, including Tor, Myc, G1 Cyclins-Cdks, Rb-E2F This acts synergistically coordinately stimulate cell cycle entry progression, protein translation, inappropriate cellular migration. In particular, fly orthologs CyclinE, Cdc25, Myc key rate-limiting required for neoplasia. Moreover, Sin1, Rictor, Cdk4 only abnormal proliferation but not development. These within may represent important therapeutic targets