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

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

Cellular and Molecular Medicine

Research output: Contribution to journal › Article › peer-review

207 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 language	English (US)
Pages (from-to)	3379-3386
Number of pages	8
Journal	Cancer Research
Volume	59
Issue number	14
State	Published - Jul 15 1999

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "Transforming growth factor β1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis",

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.",

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AU - Ormsby, Ilona

AU - Gartside, Peter S.

AU - Doetschman, Thomas

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AB - 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.

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

Abstract

ASJC Scopus subject areas

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