Transforming growth factor-beta type II receptor confers tumor suppressor activity in murine renal carcinoma (Renca) cells.
PMID 10414746 · Urology · 1999 · DOI 10.1016/s0090-4295(99)00093-x
Authors: J D Engel; S D Kundu; T Yang; S Lang; S Goodwin; L Janulis; J S Cho; J Chang; S J Kim; C Lee
Abstract
To demonstrate that the introduction of the transforming growth factor-beta (TGF-beta) type II receptor (TbetaR-II) decreases tumorigenicity in an aggressive murine renal carcinoma line, Renca. These cells do not express TbetaR-II. Because the presence of TbetaR-II in benign epithelial cells is ubiquitous, the ability to restore tumor suppressor activity in the Renca cell line with its introduction would elucidate the role of TbetaR-II as a tumor suppressor gene. Renca cells were stably transfected with a retrovirus-mediated TbetaR-II expression vector. In vitro sensitivity to growth inhibitory effect of TGF-beta was assessed by the 3H-thymidine incorporation assay. For in vivo testing, xenograft tumors were produced by subcutaneous injection of tumor cells into immunodeficient nude mice. The tumorigenicity of these TbetaR-II transfected cells was tested. Wild-type Renca cells and cells transfected with the control vector were also tested for comparison. Expression of TbetaR-II mRNA was evident in Renca cells after transfection with the TbetaR-II construct. In vitro sensitivity to the growth inhibitory effect of TGF-beta was restored. This effect of TGF-beta was reversible with a neutralizing antibody specific for the extracellular domain of TbetaR-II. Xenografts grown from TbetaR-II transfected cells were significantly smaller, weighed less, and developed tumors later than those developed from wild-type Renca cells and those transfected with the control vector. We conclude that TbetaR-II is a central mediator of tumorigenicity in Renca cells. As with other tumor suppressor genes, the loss of TbetaR-II expression allows for the development of an aggressive phenotype.
Animals; Carcinoma, Renal Cell; Cell Division; Mice; Mice, Nude; Protein Serine-Threonine Kinases; RNA, Messenger; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured
Cite
J D Engel; S D Kundu; T Yang; S Lang; S Goodwin; L Janulis; J S Cho; J Chang; S J Kim; C Lee. Transforming growth factor-beta type II receptor confers tumor suppressor activity in murine renal carcinoma (Renca) cells. Urology (1999). PMID 10414746. DOI 10.1016/s0090-4295(99)00093-x.