Smad4 (DPC4) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) β and related ligands. To directly test this hypothesis, the Smad4 gene was deleted through homologous recombination in human colorectal cancer cells. This deletion abrogated signaling from TGF-β, as well as from the TGF-β family member activin. These results provide unequivocal evidence that mutational inactivation of Smad4 causes TGF-β unresponsiveness and provide a basis for understanding the physiologic role of this gene in tumorigenesis.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Mar 3 1998|
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