Targeted deletion of Smad4 shows it is required for transforming growth factor beta and activin signaling in colorectal cancer cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 9482899.
- Also identified by PMC identifier 19358.
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Abstract
Smad4 (DPC4) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) beta 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-beta, as well as from the TGF-beta family member activin. These results provide unequivocal evidence that mutational inactivation of Smad4 causes TGF-beta unresponsiveness and provide a basis for understanding the physiologic role of this gene in tumorigenesis.
Medical subject headings
- Colorectal Neoplasms
- Gene Deletion
- Genes, Tumor Suppressor
- Inhibins
- Trans-Activators
- Transforming Growth Factor beta
- Xenopus Proteins