A model of epithelial cancer using the Drosophila egr gene in combination with the Drosophila Ras85D gene has been developed. The role of CRK family proteins in cancer has been investigated using this and related systems.
The RAS proteins are GDP/GTP-binding proteins that act as intracellular signal transducers and are crucial players in many signaling networks affecting cell cycle progression, growth, migration, cytoskeletal changes, apoptosis, and senescence. Originally defined as oncogenes, the RAS GTPase family includes KRAS (MIM:190070), HRAS (MIM:190020), and NRAS (MIM:164790); mutations in these three genes are among the most common events in human cancers. For KRAS, HRAS and NRAS, there is a single high-scoring ortholog in Drosophila, Ras85D, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. There are multiple other paralogous and orthologous genes in both species.
Tumor necrosis factor (TNF) proteins are transmembrane proteins that can be released from the cell membrane by extracellular proteolytic cleavage; they can act via both autocrine and paracrine signaling. This is a large gene family in human; in Drosophila there is a single TNF gene, eiger (egr). Animals homozygous for the loss-of-function mutation of egr1 are viable and fertile, with minor feeding and immune response phenotypes.
[updated Nov. 2024 by FlyBase; FBrf0222196]
Sole TNF family gene in Drosophila (1 Drosophila to many human); Dmel\egr is most closely related to human EDA, TNFSF13, and TNFSF13B.