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FEBS Lett. 2002 Jun 5;520(1-3):171-6.

TGF-beta(1) and Smad4 overexpression induce a less invasive phenotype in highly invasive spindle carcinoma cells.

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Laboratorio de Biologia Celular, INTA, Universidad de Chile, Casilla 138, Santiago 11, Chile.


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.

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