Open AccessTargeted deletion of Smad4 shows it is required for transforming growth factor β and activin signaling in colorectal cancer cells
Author(s) -
Shibin Zhou,
Phillip Buckhaults,
Leigh Zawel,
Fred Bunz,
Greg Riggins,
Jia Le Dai,
Scott E. Kern,
Kenneth W. Kinzler,
Bert Vogelstein
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.5.2412
Subject(s) - transforming growth factor , acvrl1 , biology , carcinogenesis , cancer research , gene , colorectal cancer , suppressor , transforming growth factor beta , signal transduction , homologous recombination , genetics , tgf beta signaling pathway , activin type 2 receptors , mutation , homologous chromosome , cancer , microbiology and biotechnology , endoglin , stem cell , cd34
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, theSmad4 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 ofSmad4 causes TGF-β unresponsiveness and provide a basis for understanding the physiologic role of this gene in tumorigenesis.