This model of epithelial cancer combines overexpression of epidermal growth factor receptor (EGFR) with reduced expression of Dmel\Socs36E, a gene involved in cytokine signalling. Dmel\Socs36E is orthologous to two human genes, SOCS4 and SOCS5, which have been shown to play a role in regulating EGF signaling. RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations caused by imprecise excision of TE insertions have been generated for Dmel\Socs36E.
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 result in dominant visible phenotypes. Egfr overexpression in imaginal disc epithelial cells leads to mild overproliferation phenotypes. Reducing expression of the Drosophila gene Socs36E also results in mild in overproliferation phenotypes. Reduced expression of Dmel\Socs36E in combination with Dmel\Egfr overexpression results in severe overgrowth and metastatic phenotypes. Dmel\Socs36E was selected as a candidate for investigation based on the fact that the levels of expression of the microRNA ban impacts the EGFR phenotypes; the Socs36E transcript is predicted to be a target of this miRNA.
See also the human disease model report 'cancer, epithelial, EGFR-microRNA-related' (FBhh0000398).
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 Dec. 2018 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]
SOCS (suppressor of cytokine signaling) family members are known to be cytokine-inducible negative regulators of cytokine signaling. SOCS4 and SOCS5 gene products impact many signaling pathways; they have been shown to inhibit EGF signaling by mediating the degradation of phosphorylated EGF receptor (EGFR). [Gene Cards, SOCS4, SOCS5; 2018.12.06]
Many to one: 2 human genes to 1 Drosophila gene.
Many to one: 2 human genes to 1 Drosophila gene.
Many to one: 4 human genes to 1 Drosophila gene.
Moderate-scoring ortholog of human SOCS5 and SOCS4 (1 Drosophila to 2 human). Dmel\Socs36E shares 33-35% identity and 46-47% similarity with the human genes.
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.
