1. Connexin43 repression following epithelium-to-mesenchyme transition in embryonal carcinoma cells requires Snail1 transcription factor
- Author
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Kristel J.M. Boonen, Marti F.A. Bierhuizen, Pieter A. Doevendans, Martin B. Rook, Toon A.B. van Veen, Bart Kok, Jacques M.T. de Bakker, Marc A. Vos, Teun P. de Boer, Marcel A.G. van der Heyden, Amsterdam Cardiovascular Sciences, and Cardiology
- Subjects
Cancer Research ,Mesenchyme ,Down-Regulation ,Fluorescent Antibody Technique ,Biology ,Transfection ,Epithelium ,Mesoderm ,Embryonal carcinoma ,Mice ,Carcinoma, Embryonal ,Cell Line, Tumor ,medicine ,Animals ,Gene silencing ,Gene Silencing ,RNA, Messenger ,RNA, Small Interfering ,Promoter Regions, Genetic ,Molecular Biology ,Psychological repression ,Transcription factor ,Embryonic Stem Cells ,Cell Biology ,medicine.disease ,Embryonic stem cell ,Molecular biology ,medicine.anatomical_structure ,Connexin 43 ,Mesoderm formation ,cardiovascular system ,Snail Family Transcription Factors ,sense organs ,biological phenomena, cell phenomena, and immunity ,Transcription Factors ,Developmental Biology - Abstract
Embryonic stem (ES) cells and embryonal carcinoma (EC) cells express high amounts of functional connexin43 (Cx43). During mesoderm formation and subsequent cardiac differentiation, Cx43 is initially down-regulated but is up-regulated again as the emerging cardiomyocytes mature. In this study, we investigated the regulation of Cx43 expression during early phases of differentiation in F9 and P19 EC cells. We found a striking inverse correlation between the expression of Cx43 and that of the transcriptional repressor Snail1. No clear relationship was found with Smad-interacting-protein1 (SIP1), another transcription factor inducing epithelium-to-mesenchyme transition (EMT). Promoter-reporter assays indicated Cx43 repression at the promoter level by ectopically expressed Snail1. To establish whether the Cx43 down-regulation depends on endogenous Snail1, MES-1 cells, differentiated derivatives of P19 EC, were stably transfected by an siRNA construct silencing Snail1 expression. This resulted in a mesenchyme-to-epithelium transition, which was accompanied by increased levels of Cx43 mRNA and protein and enhanced metabolic and electrical coupling. We conclude that Snail1-mediated EMT results in a Cx43 repression.
- Published
- 2007