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

✍ Scribed by Alessandra Turco; Anna Coppa; Simona Aloe; Gianluca Baccheschi; Stefania Morrone; Gabriella Zupi; Giulia Colletta

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 151 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990105)80:1<85::aid-ijc17>3.0.co;2-p

✦ Synopsis

Expression of type II receptor of transforming growth factor beta (T␤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␤) is associated with a decreased expression of T␤RII mRNA and protein. Reduced T␤RII expression has also been found in human thyroid differentiated and undifferentiated carcinomas. To investigate the role of T␤RII in modulating the tumorigenic potential of k-ras-transformed thyroid cells, we transfected these cells with an expression vector carrying the human T␤RII gene, regulated by an inducible promoter. Isolated clones, overexpressing T␤RII, 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 T␤RII acts as a potent tumor suppressor gene when overexpressed in malignant thyroid cells. Int.