Induction by transforming growth factor-β1 of epithelial to mesenchymal transition is a rare event in vitro
KA Brown, ME Aakre, AE Gorska, JO Price… - Breast cancer …, 2004 - Springer
KA Brown, ME Aakre, AE Gorska, JO Price, SE Eltom, JA Pietenpol, HL Moses
Breast cancer research, 2004•SpringerIntroduction 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 …
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 …
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.
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