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© The Rockefeller University Press, 0021-9525/2000/1/173/ $5.00
The Journal of Cell Biology, Volume 148, Number 1, January 10, 2000 173-188

Original Article

Epithelial Mesenchymal Transition by c-Fos Estrogen Receptor Activation Involves Nuclear Translocation of ß-Catenin and Upregulation of ß-Catenin/Lymphoid Enhancer Binding Factor-1 Transcriptional Activity

Andreas Egera, Andreas Stockingera, Birgit Schaffhausera, Hartmut Beugb, and Roland Foisnera
a Department of Biochemistry and Molecular Cell Biology, University of Vienna, A-1030 Vienna, Austria
b Research Institute of Molecular Pathology, A-1030 Vienna, Austria

Correspondence to: Roland Foisner, Department of Biochemistry and Molecular Cell Biology, Biocenter, University of Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria. Tel:43-1-4277-52856 Fax:43-1-4277-52854 E-mail:foisner{at}abc.univie.ac.at.

Mouse mammary epithelial cells expressing a fusion protein of c-Fos and the estrogen receptor (FosER) formed highly polarized epithelial cell sheets in the absence of estradiol. ß-Catenin and p120ctn were exclusively located at the lateral plasma membrane in a tight complex with the adherens junction protein, E-cadherin. Upon activation of FosER by estradiol addition, cells lost epithelial polarity within two days, giving rise to a uniform distribution of junctional proteins along the entire plasma membrane. Most of the ß-catenin and p120ctn remained in a complex with E-cadherin at the membrane, but a minor fraction of uncomplexed cytoplasmic ß-catenin increased significantly. The epithelial–mesenchymal cell conversion induced by prolonged estradiol treatment was accompanied by a complete loss of E-cadherin expression, a 70% reduction in ß-catenin protein level, and a change in the expression pattern of p120ctn isoforms. In these mesenchymal cells, ß-catenin and p120ctn were localized in the cytoplasm and in defined intranuclear structures. Furthermore, ß-catenin colocalized with transcription factor LEF-1 in the nucleus, and coprecipitated with LEF-1–related proteins from cell extracts. Accordingly, ß-catenin– dependent reporter activity was upregulated in mesenchymal cells and could be reduced by transient expression of exogenous E-cadherin. Thus, epithelial mesenchymal conversion in FosER cells may involve ß-catenin signaling.

Key Words: cell adhesion, E-cadherin, junctional complexes, polarized epithelium, wnt signaling


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