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[Cancer Research 59, 3379-3386, July 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 3379-3386, July 15, 1999]
© 1999 American Association for Cancer Research

Carcinogenesis

Transforming Growth Factor ß1 Suppresses Nonmetastatic Colon Cancer at an Early Stage of Tumorigenesis1

Sandra J. Engle2, James B. Hoying2, Gregory P. Boivin, Ilona Ormsby, Peter S. Gartside and Thomas Doetschman3

Department of Molecular Genetics, Biochemistry, and Microbiology [S. J. E., J. B. H., I. O., T. D.], Division of Comparative Pathology [G. P. B.], and Department of Environmental Health [P. S. G.], University of Cincinnati, Cincinnati, Ohio 45267

The transforming growth factor ß (TGF-ß) 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-ß1 in tumor suppression and implicates TGF-ß2 or TGF-ß3 in the prevention of metastasis. Analysis of the development of colon cancer in TGF-ß1 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-ß1 at this critical transition in the development of colon cancer.




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