Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion.
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.
Lal
Anita
A
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Glazer
Chad A
CA
Martinson
Holly M
HM
Friedman
Henry S
HS
Archer
Gary E
GE
Sampson
John H
JH
Riggins
Gregory J
GJ
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
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