This Drosophila model of malignant glioma uses the GAL4/UAS system to drive overexpression of Dmel\Egfr and Dmel\Myc in glial cells and glial precursors. 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. Mutations, overexpression, and rearrangements of MYC oncogene have also been implicated in multiple cancers (see FBhh0000402).
EGFR overexpression has been achieved by using a Dmel\Egfr fusion gene that contains a λ dimerization domain; this results in a constitutively active Egfr via forced dimerization. Overexpression of Dmel\Myc has been achieved using a wild-type transgenic copy of the gene; co-overexpression with the Egfr fusion gene induces glial neoplasia in third instar larval brains. This model system has been used to screen for genes that interact genetically to suppress or enhance the glial neoplastic phenotype; see the "Alleles Reported to Model Human Disease" section, below.
[updated Oct. 2016 by FlyBase; FBrf0222196]
Glioblastoma multiforme and other malignant gliomas are characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy (Ramirez et al., 2013; pubmed:24287492).
Glioblastoma multiforme is a malignant astrocytoma and the most common primary brain tumor among adults (reviewed in Furnari et al., 2007; pubmed:17974913).
MYC encodes a transcription factor that plays a role in cell cycle progression, apoptosis and cellular transformation. [from Gene Cards, MYC; 2016.09.30]
Many to one (3 human to 1 Drosophila); additional (lower-scoring) human orthologs are MYCN and MYCL.
Many to one (4 human to 1 Drosophila); additional human orthologs are ERBB4, ERBB3, and ERBB2.
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.
Orthologous to human gene MYC (reciprocal best hit); lower scoring ortholog of human MYCN and MYCL (1 Drosophila to 3 human). Dmel\Myc shares 31% identity and 44% similarity with human MYC, within the carboxy extents of the two proteins; the amino extents do not align.
Constructs with this fusion gene plus a λ dimerization domain and a UAS promoter produce a constitutively active Egfr via forced dimerization; expression controlled by use of different GAL4 drivers.