Abstract
We have examined the effect of transforming growth factor beta(1) (TGF-beta(1)) and overexpression of the Smad4 gene on the phenotype of Car C, a ras mutated highly malignant spindle carcinoma cell line. TGF-beta(1)-treated Car C cells overexpressing Smad4 spread with a flattened morphology with membrane ruffles abundant in vinculin and show a reduction in their invasive abilities. TGF-beta(1) treatment and overexpression of Smad4 also enhanced the production of PAI-1 measured by the activation of the p3TP-lux reporter gene containing a PAI-1-related promoter. This activation was abolished with a dominant-negative Smad4 construct. These results lead us to conclude that both TGF-beta(1) and Smad4 overexpression reduce the invasive potential of Car C cells, probably via the Smad pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma / genetics
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Carcinoma / pathology*
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Cell Movement / drug effects*
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Cell Movement / genetics
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Neoplastic
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Neoplasm Invasiveness / genetics
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Phenotype
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Trans-Activators / genetics*
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Trans-Activators / metabolism
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Transfection
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Transforming Growth Factor beta / pharmacology*
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Transforming Growth Factor beta1
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Tumor Cells, Cultured / drug effects
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Urokinase-Type Plasminogen Activator / metabolism
Substances
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DNA-Binding Proteins
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Plasminogen Activator Inhibitor 1
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Recombinant Fusion Proteins
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Trans-Activators
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Urokinase-Type Plasminogen Activator