Abstract
The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells from a variety of apoptotic injuries. In several instances, the anti-apoptotic effect of the wild type IGF-IR is more evident under conditions of anchorage-independence than in cells in monolayer cultures. We have investigated IGF-IR signaling in cells in anoikis, a form of apoptosis that occurs when cells are denied attachment to the extra-cellular matrix. IGF-I protects mouse embryo fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival is dependent on the concentration of IGF-I and a sufficient number of functional IGF-I receptors. In this model, IGF-I protection correlates best with ras activation and cell-to-cell aggregation, while PI3-kinase, Akt and MAP kinases seem to play a lesser, alternative role.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Androstadienes / pharmacology
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Animals
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Apoptosis*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Survival
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Chromones / pharmacology
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Enzyme Inhibitors / pharmacology
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Extracellular Matrix / metabolism
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Humans
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Insulin-Like Growth Factor I / metabolism
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Insulin-Like Growth Factor I / pharmacology
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Morpholines / pharmacology
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Oncogene Protein v-akt
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Polyhydroxyethyl Methacrylate
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / metabolism*
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Retroviridae Proteins, Oncogenic / genetics
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Retroviridae Proteins, Oncogenic / metabolism
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Signal Transduction*
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Wortmannin
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ras Proteins / metabolism
Substances
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Androstadienes
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Chromones
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Enzyme Inhibitors
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Retroviridae Proteins, Oncogenic
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Polyhydroxyethyl Methacrylate
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1
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Oncogene Protein v-akt
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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ras Proteins
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Wortmannin