Overexpression of transforming growth factor β-type II receptor reduces tumorigenicity and metastastic potential of K-ras-transformed thyroid cells

Expression of type II receptor of transforming growth factor beta (TβRII) 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 (TGFβ) is associated with a decreased expression of TβRII mRNA and protein. Reduced TβRII expression has also been found in human thyroid differentiated and undifferentiated carcinomas. To investigate the role of TβRII in modulating the tumorigenic potential of k-ras-transformed thyroid cells, we transfected these cells with an expression vector carrying the human TβRII gene, regulated by an inducible promoter. Isolated clones, overexpressing TβRII, showed a reduction in the anchorage-dependent and -independent cell growth, compared with control k-ras-transformed cells. When transplanted in athymic nude mice, the transfected clones presented a decrease in tumorigenicity with respect to the highly malignant parental cells. Moreover, the diminished tumorigenic ability of the clones studied was accompanied by a statistically significant reduction in spontaneous and lung artificial metastases. Taken together, our data demonstrate that TβRII acts as a potent tumor suppressor gene when overexpressed in malignant thyroid cells. Int. J. Cancer 80:85–91, 1999. © 1999 Wiley-Liss, Inc.