TGF-beta(1) and Smad4 overexpression induce a less invasive phenotype in highly invasive spindle carcinoma cells.
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.
Santibáñez
Juan Francisco
JF
Laboratorio de Biologia Celular, INTA, Universidad de Chile, Casilla 138, Santiago 11, Chile. jfsantib@uec.inta.uchile.cl
Quintanilla
Miguel
M
Martínez
Jorge
J
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D004268:DNA-Binding Proteins; D017395:Plasminogen Activator Inhibitor 1; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator