This model of epithelial cancer combines overexpression of epidermal growth factor receptor (Dmel\Egfr) with overexpression of Dmel\trol. Overexpression of both Dmel\trol and Dmel\Egfr in wing discs results in an extreme overgrowth phenotype and neoplastic transformation; intermingling of epithelial and mesenchymal populations is observed.
Dmel\trol is orthologous to the human gene HSPG2, which encodes perlecan, a heparan sulfate proteoglycan that is a major component of basement membranes. Many classical loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\trol.
Animals homozygous for loss-of-functions mutations of Dmel\trol typically die in the larval or pupal stage, with smaller imaginal discs and morphological neural defects. Overexpression of trol in the wing disc (without coexpression of Egfr) has little effect on growth of the disc.
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.
See also the human disease model report 'cancer, epithelial, EGFR-related' (FBhh0000932).
[updated May 2019 by FlyBase; FBrf0222196]
HSPG2 encodes the perlecan protein, which consists of a core protein to which three long chains of glycosaminoglycans (heparan sulfate or chondroitin sulfate) are attached. Perlecan is a major component of basement membranes; binds to and cross-links many extracellular matrix components and cell-surface molecules; helps to maintain the endothelial barrier function. [Gene Cards, HSPG2; 2019.05.15]
Many to one: 4 human genes to 1 Drosophila gene.
One to one: 1 human gene to 1 Drosophila gene.
Moderate-scoring ortholog of human HSPG2 (1 Drosophila to 1 human). Dmel\trol shares 24% identity and 35% similarity with the human 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.
