Transforming growth factor β1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis

Sandra J. Engle, James B. Hoying, Gregory P. Boivin, Ilona Ormsby, Peter S. Gartside, Thomas Doetschman

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

The transforming growth factor β (TGF-β) pathway is known to play an important role in both human and murine colon cancer. However, the staging, ligand specificity, and mechanism underlying the tumor suppressive activity of this pathway are unknown. We developed a mouse model for colon cancer that identifies an early role for TGF-β1 in tumor suppression and implicates TGF- β2 or TGF-β3 in the prevention of metastasis. Analysis of the development of colon cancer in TGF-β1 knockout mice pinpoints the defect to the hyperplasty/adenoma transition and reveals that the mechanism involves an inability to maintain epithelial tissue organization and not a loss of growth control, increased inflammatory activity, or increased genetic instability. These mice provide a unique opportunity to investigate the specific role of TGF-β1 at this critical transition in the development of colon cancer.

Original languageEnglish (US)
Pages (from-to)3379-3386
Number of pages8
JournalCancer Research
Volume59
Issue number14
StatePublished - Jul 15 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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