Transforming growth factor beta 1 suppresses nonmetastatic colon cancer atan early stage of tumorigenesis

The transforming growth factor beta (TGF-beta) 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 activit y of this pathway are unknown. We developed a mouse model for colon cancer that identifies an early role for TGF-beta 1 in tumor suppression and impli cates TGF-beta 2 or TGF-beta 3 in the prevention of metastasis, Analysis of the development of colon cancer in TGF-beta 1 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 gene tic instability. These mice provide a unique opportunity to investigate the specific role of TGF-beta 1 at this critical transition in the development of colon cancer.