Abstract
NIH-3T3 fibroblasts expressing epidermal growth factor receptors (EGFRs) lacking the actin binding domain (ABD) were analyzed for their EGF-induced capacity to invade a bone marrow stromal cell (BMSC) monolayer. The fibroblasts display a reduction in the percentage of cytoskeleton-associated EGFRs. Furthermore, EGF-induced tyrosine kinase activity is unaffected by the mutation. Cells expressing the mutant EGFRs hardly invade a BMSC monolayer upon EGF stimulation in contrast to cells expressing wild-type EGFRs. Using the same cells no difference was observed in PDGF-induced invasion, which ligand was as potent in both cell types as EGF was in wild-type cells. Inhibition of both the phosphatidyl inositol-3-kinase (PI-3-K) and lipoxygenase pathways in wild-type cells mimicked the effect of the ABD deletion. Our results point to an important role for the ABD of the EGFR in EGF-induced tissue invasion.
MeSH terms
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3T3 Cells
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Actins / metabolism*
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Androstadienes / pharmacology
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Animals
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Binding Sites
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Bone Marrow Cells*
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Cell Adhesion / physiology
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Cell Movement / physiology*
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Cells, Cultured
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Coculture Techniques
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Cytoskeleton / metabolism
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Humans
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Lipoxygenase Inhibitors / pharmacology
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Masoprocol / pharmacology
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Mice
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Neoplasm Invasiveness
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / physiology
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Platelet-Derived Growth Factor / pharmacology
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Protein-Tyrosine Kinases / metabolism
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Signal Transduction / physiology
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Wortmannin
Substances
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Actins
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Androstadienes
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Enzyme Inhibitors
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Lipoxygenase Inhibitors
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Platelet-Derived Growth Factor
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Epidermal Growth Factor
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Masoprocol
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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ErbB Receptors
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Protein-Tyrosine Kinases
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Wortmannin