Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro.
Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro.
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DOI：
10.1186/bcr778
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Moses HL
中科院分区：
文献类型：
--
作者：
Brown KA;Aakre ME;Gorska AE;Price JO;Eltom SE;Pietenpol JA;Moses HL
转化生长因子（Transforming growth factor，TGF）-β1在肿瘤发生早期抑制上皮细胞的生长，在肿瘤发生后期通过诱导上皮细胞向间质细胞转化（epithelial to mesenchymal transition，EMT）促进肿瘤细胞的运动和侵袭。EMT是一个多步骤的过程，其特征在于细胞形态的变化和细胞-细胞接触的解离。尽管人们对TGF-β1介导的EMT越来越感兴趣，但其表型仅限于少数小鼠细胞系和小鼠模型。为了确定研究TGF-β1诱导的EMT的替代细胞系统，通过分析细胞形态和闭合小带-1、E-钙粘蛋白和F-肌动蛋白的定位，筛选了18种人和小鼠建立的细胞系和两种人原代上皮细胞类型的培养物，以确定TGF-β1诱导的EMT。还通过[3 H]胸苷掺入、流式细胞术、Smad 2磷酸化以及这些细胞系和另外六种癌细胞系中Smad 2和Smad 3的总水平来确定对TGF-β1的敏感性。TGF-β1对大多数非转化细胞的生长有抑制作用，但许多癌细胞对TGF-β1的生长抑制作用不敏感。相反，TGF-β1在大多数细胞系中诱导Smad 2磷酸化，包括对TGF-β1介导的细胞周期停滞具有抗性的细胞系。在筛选的细胞系中，只有两个经历了TGF-β1诱导的EMT。本文提供的结果表明，尽管许多癌细胞系对TGF-β1的生长抑制作用失去了敏感性，但大多数显示出TGF-β1信号转导的证据，但只有少数细胞系经历TGF-β1介导的EMT。
Transforming growth factor (TGF)-β1 is proposed to inhibit the growth of epithelial cells in early tumorigenesis, and to promote tumor cell motility and invasion in the later stages of carcinogenesis through the induction of an epithelial to mesenchymal transition (EMT). EMT is a multistep process that is characterized by changes in cell morphology and dissociation of cell–cell contacts. Although there is growing interest in TGF-β1-mediated EMT, the phenotype is limited to only a few murine cell lines and mouse models. To identify alternative cell systems in which to study TGF-β1-induced EMT, 18 human and mouse established cell lines and cultures of two human primary epithelial cell types were screened for TGF-β1-induced EMT by analysis of cell morphology, and localization of zonula occludens-1, E-cadherin, and F-actin. Sensitivity to TGF-β1 was also determined by [3H]thymidine incorporation, flow cytometry, phosphorylation of Smad2, and total levels of Smad2 and Smad3 in these cell lines and in six additional cancer cell lines. TGF-β1 inhibited the growth of most nontransformed cells screened, but many of the cancer cell lines were insensitive to the growth inhibitory effects of TGF-β1. In contrast, TGF-β1 induced Smad2 phosphorylation in the majority of cell lines, including cell lines resistant to TGF-β1-mediated cell cycle arrest. Of the cell lines screened only two underwent TGF-β1-induced EMT. The results presented herein show that, although many cancer cell lines have lost sensitivity to the growth inhibitory effect of TGF-β1, most show evidence of TGF-β1 signal transduction, but only a few cell lines undergo TGF-β1-mediated EMT.
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影响因子：
64.5
作者：
Eppert, K;Scherer, SW;Attisano, L
通讯作者：
Attisano, L
DOI：
10.1083/jcb.118.3.715
发表时间：
1992-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Arrick BA;Lopez AR;Elfman F;Ebner R;Damsky CH;Derynck R
通讯作者：
Derynck R
DOI：
10.1006/bbrc.1998.9170
发表时间：
1998-08-19
影响因子：
3.1
作者：
Afrakhte, M;Morén, A;ten Dijke, P
通讯作者：
ten Dijke, P
影响因子：
4.8
作者：
Ebisawa, T;Fukuchi, M;Miyazono, K
通讯作者：
Miyazono, K
影响因子：
3.7
作者：
Fujimoto, K;Sheng, H;Beauchamp, RD
通讯作者：
Beauchamp, RD