Analysis of TGF-beta receptors in malignant glioma cells

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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.