Targeted deletion of Smad4 shows it is required for transforming growth factor β and activin signaling in colorectal cancer cells

Shibin Zhou, Phillip Buckhaults, Leigh Zawel, Fred Bunz, Greg Riggins, Jia Le Dai, Scott E. Kern, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)2412-2416
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number5
DOIs
StatePublished - Mar 3 1998

ASJC Scopus subject areas

  • General

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