Epidermal growth factor receptor (EGFR) has been implicated in multiple cancers (see FBhh0000398); more than 40% of glioblastomas show amplification and/or mutation of EGFR. The gene encodes a transmembrane receptor kinase that spans the cell membrane and is activated by a number of external ligands, including EGF and transforming growth factor α. Activation of EGFR initiates several signal transduction cascades, leading to DNA synthesis and cell proliferation. There is one orthologous gene in flies, Dmel\Egfr, for which classical amorphic and hypomorphic alleles, constitutively active alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Egfr is orthologous to three additional human genes, ERBB4, ERBB3 and ERBB2. ERBBS has also been implicated in multiple cancers, including glioma susceptibility 1 (OMIM:137800).
The human gene Hsap\EGFR has been introduced into flies, using a mutant form that displays constitutive kinase activity and can be expressed in specific tissues using the GAL4-UAS system. Using a GAL4 construct that drives expression in glial cells, glial overgrowth, brain enlargement and lethality at third instar larval stage are observed; this genotype recapitulates some aspects of glioma. Overexpressing, in addition, a transgenic copy of Dmel\Pi3K92E results in a more robust model of malignant glioma in Drosophila (see FBhh0000401).
[updated Oct. 2016 by FlyBase; FBrf0222196]
More than 40% of glioblastomas (GBMs) show EGFR gene amplification, and these amplification events are often accompanied by mutations in EGFR; the most prevalent mutant form of EGFR is an intragenic truncation mutant that displays constitutive kinase activity (reviewed in Furnari et al., 2007; pubmed:17974913).
Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ErbB family. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Binding of DGFR can activate at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. [from Gene Cards, EGFR; 2016.09.30]
Many to one (4 human to 1 Drosophila); additional human orthologs are ERBB4, ERBB3, and ERBB2.