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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Enzyme Inhibitors / pharmacology
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / biosynthesis
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ErbB Receptors / genetics
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ErbB Receptors / physiology*
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Extracellular Matrix Proteins / biosynthesis
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Extracellular Matrix Proteins / genetics*
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / drug effects
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Glioblastoma / genetics*
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Glioblastoma / metabolism
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Glioblastoma / pathology
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Humans
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Metalloendopeptidases / biosynthesis
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Metalloendopeptidases / genetics
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Mice
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Mice, Nude
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Neoplasm Invasiveness
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Quinazolines
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Reverse Transcriptase Polymerase Chain Reaction
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Serine Endopeptidases / biosynthesis
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Serine Endopeptidases / genetics
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Transfection
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Tumor Cells, Cultured
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Tyrphostins / pharmacology
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Up-Regulation
Substances
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Enzyme Inhibitors
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Extracellular Matrix Proteins
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Quinazolines
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Tyrphostins
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epidermal growth factor receptor VIII
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RTKI cpd
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ErbB Receptors
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Serine Endopeptidases
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Metalloendopeptidases