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Modelling glioma growth and invasion in Drosophila
Author(s) -
Paulus Werner,
Witte Hanna,
Jeibmann Astrid,
Klaembt Christian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.172.6
Subject(s) - biology , tsc1 , imaginal disc , drosophila melanogaster , receptor tyrosine kinase , cancer research , microbiology and biotechnology , glioma , rheb , wortmannin , pi3k/akt/mtor pathway , kinase , signal transduction , gene , genetics , mtorc1
Drosophila melanogaster model systems are characterized by easy handling, rapid generation time, and a wide armamentarium of genetic techniques. Furthermore, many molecular pathways are highly conserved between invertebrates and humans. While fly models have been established for type 1 neurofibromatosis, tuberous sclerosis and neurodegenerative disorders, no fly model of glioma is available so far. Using the Gal4‐UAS system we have produced several lines of transgenic flies by overexpression or RNAi‐mediated inactivation of homologs of human “glioma genes” (EGFR, PI3K, TP53, PTEN, PDGFR and RAS genes) under control of the glia‐specific promoter reversed polarity (repo). Glial expression of activated Egfr, activated Pvr (PDGFR and VEGFR homolog), wild type Pi3k and wild type Ras2 resulted in markedly increased numbers of glial cells as determined by morphometry of eye imaginal disk and optic stalk glia of 3 rd instar larvae. Remarkably, glial cells ectopically migrated along nerve tracts. Larval lines overexpressing activated EGFR and Pvr showed fused brain lobes and thickened peripheral nerves. Administration of the EGFR tyrosine kinase inbibitor gefitinib and the PI3 kinase inhibitor wortmannin reverted larval neuropathology. These Drosophila models should be useful in genetic screens for revealing interacting genes involved in gliomagenesis, as well as in experimental therapy approaches.