Human epidermal growth factor receptor (EGFR) has been implicated in multiple cancers of epithelial derivation. EGFR is 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; ERBB2 has also been implicated in multiple cancers.
Amorphic mutations of Dmel\Egfr act as recessive embryonic lethals; they also act as cell lethals in somatic clones. Hypermorphic (gain-of-function) alleles exhibit dominant visible phenotypes. Egfr overexpression in imaginal disc epithelial cells leads to mild overproliferation phenotypes; the mild phenotype has been exploited to screen for enhancement by interacting genes. A transgenic allele that is constitutively active (FBal0065871) has also been used in this disease model. Extensive physical and genetic interactions have been described; see below and in the gene report for Egfr.
When more glucose is available to Egfr-overexpressing cells by either overexpression of the glucose transporter Glut1 or by feeding the larvae a high-sugar diet, the hyperplasia phenotype advances to neoplasia. See also the human disease model report 'cancer, multiple, RAS-CSK(SRC)-related with high-sugar diet' (FBhh0000665).
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. Constructs of Hsap\EGFR have been used for human disease models of malignant glioma (FBhh0000399, FBhh0000401, FBhh0000403).
[updated Jul. 2021 by FlyBase; FBrf0222196]
Epidermal growth factor receptor (EGFR) has been implicated in multiple cancers, including non-small-cell lung cancer (MIM:211980). [from MIM:131550; 2016.09.30]
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 genes to 1 Drosophila gene.
Orthologous to human genes EGFR, ERBB4, ERBB3, and ERBB2 (1 Drosophila to 4 human). Dmel\Egfr shares 33-37% identity and 46-51% similarity with the human genes.
