Transforming growth factor-beta type II receptor confers tumor suppressor activity in murine renal carcinoma (renca) cells

Abstract

Objectives. To demonstrate that the introduction of the transforming growth factor-beta (TGF-β) type II receptor (TβR-II) decreases tumorigenicity in an aggressive murine renal carcinoma line, Renca. These cells do not express TβR-II. Because the presence of TβR-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 TβR-II as a tumor suppressor gene. Methods. Renca cells were stably transfected with a retrovirus-mediated TβR-II expression vector. In vitro sensitivity to growth inhibitory effect of TGF-β 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 TβR-II transfected cells was tested. Wild-type Renca cells and cells transfected with the control vector were also tested for comparison. Results. Expression of TβR-II mRNA was evident in Renca cells after transfection with the TβR-II construct. In vitro sensitivity to the growth inhibitory effect of TGF-β was restored. This effect of TGF-β was reversible with a neutralizing antibody specific for the extracellular domain of TβR-II. Xenografts grown from TβR-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. Conclusions. We conclude that TβR-II is a central mediator of tumorigenicity in Renca cells. As with other tumor suppressor genes, the loss of TβR-II expression allows for the development of an aggressive phenotype.