Absence of expression of transforming growth factor-beta type II receptor is associated with an aggressive growth pattern in a murine renal carcinoma cell line, Renca

Transforming growth factor-beta1 (TGF-beta1) inhibits the proliferation of many cancer cells. However, tumor cells frequently become resistant to this inhibitory effect due to the absence of TGF-beta receptor (TbetaR) expression. This study reports the nature of TGF-beta sensitivity in an aggressive murine renal carcinoma cell line, Renca, investigated in a series of experiments. The growth of Renca cells, in tissue culture, was not sensitive to the inhibitory effect of TGF-beta1 with doses ranging from 0.1 to 10 ng./ml., nor was this cell line sensitive to the effect of TGF-beta1 in inducing the expression of plasminogen activator inhibitor-I. Renca cells expressed TGF-beta1 mRNA and protein, as determined by RT-PCR and ELISA, respectively. The level of TGF-beta1 production by Renca cells was moderate, thus eliminating the possibility that endogenous TGF-beta1 production might be masking the effect of TGF-beta sensitivity. Furthermore, Renca cells expressed TbetaR-I mRNA, but did not express TbetaR-II mRNA, suggesting that the absence of this receptor may be the cause of TGF-beta insensitivity. Additionally, a vector containing the TbetaR-II cDNA was transiently transfected into Renca cells. The inhibitory effect of TGF-beta1 was introduced in Renca cells after transfection with this receptor. At the same time, the growth rate of these cells diminished significantly when compared with that of the wild type Renca cells, as judged by the rate of [3H]-thymidine incorporation in the absence of any exogenous TGF-beta1. These observations demonstrated that Renca cells lack the functional TbetaR-II and suggest that their aggressive growth pattern is due, at least in part, to their insensitivity to TGF-beta.