Abstract
ATF3 stimulated promoter activity of EphA1 by 3.4-fold in ATF3-dependent angiogenesis in vitro. Although tyrosine kinase activation of EphA1 was dispensable, binding of EphA1 to fibronectin through its type I repeat played an essential role in the angiogenesis. Recombinant proteins containing fibronectin 10th to 12th type I repeat (I 10-12) but not I 12 could inhibit the angiogenesis in vitro by competitively targeting EphA1 with the full-length fibronectin. However, I 12 acquired a higher affinity toward EphA2 with K(d) 18 nm and inhibited vascular endothelial growth factor-dependent angiogenic invasion in a Matrigel plug assay.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 3 / genetics
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Activating Transcription Factor 3 / metabolism*
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Doxorubicin / pharmacology
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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Fibronectins / metabolism*
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Humans
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Ligands
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Mice
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Mice, Inbred C57BL
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Mice, Nude
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Neoplasms / blood supply
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Pathologic / pathology
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Protein Binding
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Rats
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Receptor, EphA1 / genetics
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Receptor, EphA1 / metabolism*
Substances
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Activating Transcription Factor 3
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Fibronectins
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Ligands
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Doxorubicin
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Receptor, EphA1