INACTIVATION OF THE TYPE-II TGF-BETA RECEPTOR IN COLON-CANCER CELLS WITH MICROSATELLITE INSTABILITY

Transforming growth factor-beta (TGF-beta) is a potent inhibitor of ep ithelial cell growth. Human colon cancer cell lines with high rates of microsatellite instability were found to harbor mutations in the type II TGF-beta receptor (RII) gene. Eight such examples, due to three di fferent mutations, were identified. The mutations were clustered withi n small repeated sequences in the RII gene, were accompanied by the ab sence of cell surface RII receptors, and were usually associated with small amounts of RII transcript. RII mutation, by inducing the escape of cells from TGF-beta-mediated growth control, links DNA repair defec ts with a specific pathway of tumor progression.