期刊论文详细信息
Breast Cancer Research
Induction by transforming growth factor-β1 of epithelial to mesenchymal transition is a rare event in vitro
Harold L Moses3  Jennifer A Pietenpol2  Sakina E Eltom4  James O Price1  Agnieska E Gorska3  Mary E Aakre3  Kimberly A Brown3 
[1] Veterans Affairs Medical Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA;Department of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee, USA;Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA;Department of Pharmacology, Meharry Medical College, Nashville, Tennessee, USA
关键词: ZO-1;    TGF-β1;    Smad;    epithelial to mesenchymal transition;    E-cadherin;   
 received in 2003-05-21, accepted in 2004-02-20,  发布年份 2004
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【 摘 要 】

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

【 授权许可】

   
2004 Brown et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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