Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro.

Brown KA, Aakre ME, Gorska AE, Price JO, Eltom SE, Pietenpol JA, Moses HL
Breast Cancer Res. 2004 6 (3): R215-31

PMID: 15084245 · PMCID: PMC400675 · DOI:10.1186/bcr778

INTRODUCTION - Transforming growth factor (TGF)-beta1 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-beta1-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-beta1-induced EMT, 18 human and mouse established cell lines and cultures of two human primary epithelial cell types were screened for TGF-beta1-induced EMT by analysis of cell morphology, and localization of zonula occludens-1, E-cadherin, and F-actin. Sensitivity to TGF-beta1 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-beta1 inhibited the growth of most nontransformed cells screened, but many of the cancer cell lines were insensitive to the growth inhibitory effects of TGF-beta1. In contrast, TGF-beta1 induced Smad2 phosphorylation in the majority of cell lines, including cell lines resistant to TGF-beta1-mediated cell cycle arrest. Of the cell lines screened only two underwent TGF-beta1-induced EMT.

CONCLUSION - The results presented herein show that, although many cancer cell lines have lost sensitivity to the growth inhibitory effect of TGF-beta1, most show evidence of TGF-beta1 signal transduction, but only a few cell lines undergo TGF-beta1-mediated EMT.

MeSH Terms (29)

Actins Animals Cadherins Cell Adhesion Cell Cycle Cell Line, Transformed Cell Line, Tumor Cell Movement Cells, Cultured Disease Progression DNA-Binding Proteins Epithelial Cells Humans In Vitro Techniques Membrane Proteins Mesoderm Mice Neoplasm Invasiveness Neoplasm Proteins Phenotype Phosphoproteins Phosphorylation Protein Processing, Post-Translational Smad2 Protein Smad3 Protein Trans-Activators Transforming Growth Factor beta Transforming Growth Factor beta1 Zonula Occludens-1 Protein

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