Kundu S D, Kim I Y, Zelner D, Janulis L, Goodwin S, Engel J D, Lee C
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J Urol. 1998 Nov;160(5):1883-8.
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.
转化生长因子-β1（TGF-β1）可抑制多种癌细胞的增殖。然而，由于缺乏TGF-β受体（TβR）表达，肿瘤细胞常常对这种抑制作用产生抗性。本研究报告了在一系列实验中对侵袭性小鼠肾癌细胞系Renca中TGF-β敏感性的研究结果。在组织培养中，Renca细胞的生长对0.1至10 ng/ml剂量的TGF-β1的抑制作用不敏感，该细胞系对TGF-β1诱导纤溶酶原激活物抑制剂-I表达的作用也不敏感。分别通过逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）确定，Renca细胞表达TGF-β1 mRNA和蛋白。Renca细胞产生的TGF-β1水平适中，因此排除了内源性TGF-β1产生可能掩盖TGF-β敏感性效应的可能性。此外，Renca细胞表达TβR-I mRNA，但不表达TβR-II mRNA，这表明该受体的缺失可能是TGF-β不敏感的原因。另外，将含有TβR-II cDNA的载体瞬时转染到Renca细胞中。转染该受体后，TGF-β1的抑制作用在Renca细胞中得以体现。同时，在没有任何外源性TGF-β1的情况下，通过[3H]-胸苷掺入率判断，与野生型Renca细胞相比，这些细胞的生长速率显著降低。这些观察结果表明，Renca细胞缺乏功能性TβR-II，并提示它们的侵袭性生长模式至少部分归因于对TGF-β不敏感。
