Analysis of TGF-beta receptors in malignant glioma cells

我们研究了8种恶性胶质瘤细胞系对转化生长因子-β（TGF-β）体外生长抑制活性的反应以及恶性胶质瘤细胞中TGF-β I型和II型受体的表达。然后，我们研究了TGF-β对p27 Kip 1细胞周期蛋白依赖性激酶抑制剂表达的影响，以评估TGF-β受体的下游信号传递。所有恶性胶质瘤细胞系对TGF-β 1和TGF-β 2的生长抑制不敏感。通过使用125 I-TGF-β 1的亲和标记分析TGF-β受体，显示6个胶质瘤细胞系在其细胞表面上具有TGF-β I型和II型受体，而2个肿瘤细胞系具有非常少量的TGF-β I型和/或II型受体。北方印迹分析显示，所有肿瘤细胞系均表达TGF-β I型和II型受体的信使核糖核酸。流式细胞术分析显示，TGF-β 1处理恶性胶质瘤细胞后，除一株胶质瘤细胞系外，所有恶性胶质瘤细胞系中p27 Kip 1蛋白的表达均显著下调，这些数据表明，大多数恶性胶质瘤细胞表达TGF-β I型和II型受体，这些受体可以向下游传递一些信号，对TGF-β生长抑制反应的丧失可能不是由于TGF-β受体本身的异常。

We investigated the response of 8 malignant glioma cell lines to the growth inhibitory activity of transforming growth factor-beta (TGF-beta) in vitro and the expression of TGF-beta type I and type II receptors in malingnant glioma cells. We then investigated the effect of TGF-beta on the expression of a p27Kip1 cyclin-dependent kinase inhibitor to assess a downstream signal transmission from TGF-beta receptors. All malignant glioma cell lines were insensitive to growth inhibition by TGF-beta1 and TGF-beta2. Analysis of TGF-beta receptors by affinity labeling using 125I-TGF-beta1 showed 6 glioma lines had both TGF-beta type I and type II receptors on their cell surfaces, while 2 tumor lines had very small amount of TGF-beta type I and/or type II receptors. Northern blot analysis showed all tumor lines expressed messsenger ribonucleic acids for both TGF-beta type I and II receptors in variable levels. Flow cytometric analyzes revealed that treatment of malignant glioma cells with TGF-beta1 downregulated significantly the sxpression of p27Kip1 protein in all malignant glioma cell lines, except in one glioma line.These data suggest that most malignant glioma cells express TGF-beta type I and type II receptors that can transmit some siganls downstream, and that loss of response to TGF-beta growth inhibition may not be due to the abnormality of TGF-beta receptors themselves.