title: Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion.
abstract: The gene most commonly altered in human glioblastomas is the epidermalgrowth factor receptor (EGFR). We profiled transcripts induced by mutantEGFR to better understand its role in tumor progression. The pattern found suggested enhanced tumor invasion. The highly induced genes included extracellular matrix components, metalloproteases, and a serine protease. We confirmed that mutant EGFR did make glioblastoma cells both more motile and invasive using in vitro assays. Furthermore, inhibitors of EGFR (OSI-774 and Tyrphostin AG1478) selectively down-regulated these molecular effectors in glioblastoma cells, eliminating enhanced invasion.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Lal
authors.forename: Chad A
authors.initials: CA
authors.lastname: Glazer
authors.forename: Holly M
authors.initials: HM
authors.lastname: Martinson
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Gary E
authors.initials: GE
authors.lastname: Archer
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011799:Quinazolines; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D011799:Quinazolines; D020032:Tyrphostins; C410723:epidermal growth factor receptor VIII; C101044:RTKI cpd; D066246:ErbB Receptors; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases