OVEREXPRESSION OF TRANSFORMING-GROWTH-FACTOR BETA-TYPE II RECEPTOR REDUCES TUMORIGENICITY AND METASTASTIC POTENTIAL OF K-RAS-TRANSFORMED THYROID-CELLS

Expression of type II receptor of transforming growth factor beta (T b eta RII) is necessary for this factor to inhibit the growth of thyroid epithelial cells. In rat thyroid transformed cells, the resistance to transforming growth factor beta (TGF beta) is associated with a decre ased expression of T beta RII mRNA and protein. Reduced T beta RII exp ression has also been found in human thyroid differentiated and undiff erentiated carcinomas. To investigate the role of T beta RII in modula ting the tumorigenic potential of k-ras-transformed thyroid cells, we transfected these cells with an expression vector carrying the human T beta RII gene, regulated by an inducible promoter. Isolated clones, o verexpressing T beta RII, showed a reduction in the anchorage-dependen t and -independent cell growth, compared with control k-ras-transforme d cells. When transplanted in athymic nude mice, the transfected clone s presented a decrease in tumorigenicity with respect to the highly ma lignant parental cells. Moreover, the diminished tumorigenic ability o f the clones studied was accompanied by a statistically significant re duction in spontaneous and lung artificial metastases. Taken together, our data demonstrate that T beta RII acts as a potent tumor suppresso r gene when overexpressed in malignant thyroid cells. (C) 1999 Wiley-L iss, Inc.