首页> 外文期刊>Molecular and Cellular Endocrinology >Lack of responsiveness to TGF-beta1 in a thyroid carcinoma cell line with functional type I and type II TGF-beta receptors and Smad proteins, suggests a novel mechanism for TGF-beta insensitivity in carcinoma cells.
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Lack of responsiveness to TGF-beta1 in a thyroid carcinoma cell line with functional type I and type II TGF-beta receptors and Smad proteins, suggests a novel mechanism for TGF-beta insensitivity in carcinoma cells.

机译:具有功能性I型和II型TGF-β受体和Smad蛋白的甲状腺癌细胞系中对TGF-β1缺乏响应性,提示癌细胞中TGF-β不敏感的新机制。

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摘要

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine. In the present study we have investigated the expression of TGF-beta receptors (TbetaR's) and SMAD proteins in non-neoplastic and neoplastic thyroid follicle cells. We found expression of all TbetaR's (type I, II and III) and SMAD proteins analysed (Smad2, Smad3, Smad4, Smad6 and Smad7). Five out of six human anaplastic thyroid carcinoma cell lines were growth inhibited by addition of TGF-beta1, and therefore considered to be TGF-responsive. One cell line however, HTh 7, did not respond to TGF-beta1 with growth inhibition, induction of the extracellular matrix protein fibronectin or immediate early genes junB, Smad6 and Smad7 mRNA. Analysis of the TGF-beta intracellular signalling pathway in HTh 7 cells showed that receptors were capable of signalling, e.g. Smad2 phosphorylation and SMAD nuclear translocation. In summary, our data shows abundant expression of TGF-beta signalling components in thyroid follicle cells, and the escape from TGF-beta sensitivity in one anaplastic thyroid carcinoma despite an apparently functional TGF-beta/SMAD-signalling pathway, indicating a novel mechanism for TGF-beta insensitivity.
机译:转化生长因子-β(TGF-β)是一种多功能的细胞因子。在本研究中,我们研究了TGF-β受体(TbetaR's)和SMAD蛋白在非肿瘤和肿瘤性甲状腺滤泡细胞中的表达。我们发现所有TbetaR(I型,II型和III型)和SMAD蛋白(Smad2,Smad3,Smad4,Smad6和Smad7)的表达。六种人类变性甲状腺癌癌细胞系中有五种被添加TGF-beta1抑制生长,因此被认为是TGF反应性的。然而,一种细胞系HTh 7对TGF-β1没有生长抑制,细胞外基质蛋白纤连蛋白或立即早期基因junB,Smad6和Smad7 mRNA的诱导反应。对HTh 7细胞中TGF-β细胞内信号转导通路的分析表明,受体能够发信号,例如: Smad2磷酸化和SMAD核易位。总而言之,我们的数据显示,尽管有明显的功能性TGF-β/ SMAD信号通路,但在甲状腺未分化的甲状腺癌中TGF-β信号传导成分在甲状腺滤泡细胞中大量表达,并逃脱了TGF-β敏感性。 TGF-β不敏感。

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