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TGF‐β 1 and Smad4 overexpression induce a less invasive phenotype in highly invasive spindle carcinoma cells
Author(s) -
Santibáñez Juan Francisco,
Quintanilla Miguel,
Martı́nez Jorge
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02760-6
Subject(s) - smad , phenotype , transforming growth factor , transforming growth factor beta , cell culture , cancer research , biology , tgf beta signaling pathway , gene , microbiology and biotechnology , chemistry , genetics
We have examined the effect of transforming growth factor β 1 (TGF‐β 1 ) and overexpression of the Smad4 gene on the phenotype of Car C, a ras mutated highly malignant spindle carcinoma cell line. TGF‐β 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‐β 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‐β 1 and Smad4 overexpression reduce the invasive potential of Car C cells, probably via the Smad pathway.