Epithelial mesenchymal transition by c-Fos estrogen receptor activation involves nuclear translocation of beta-catenin and upregulation of beta-catenin/lymphoid enhancer binding factor-1 transcriptional activity.
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. Beta-catenin and p120(ctn) 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 beta-catenin and p120(ctn) remained in a complex with E-cadherin at the membrane, but a minor fraction of uncomplexed cytoplasmic beta-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 beta-catenin protein level, and a change in the expression pattern of p120(ctn) isoforms. In these mesenchymal cells, beta-catenin and p120(ctn) were localized in the cytoplasm and in defined intranuclear structures. Furthermore, beta-catenin colocalized with transcription factor LEF-1 in the nucleus, and coprecipitated with LEF-1-related proteins from cell extracts. Accordingly, beta-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 beta-catenin signaling.
Eger
A
A
Department of Biochemistry and Molecular Cell Biology, University of Vienna, A-1030 Vienna, Austria.
Stockinger
A
A
Schaffhauser
B
B
Beug
H
H
Foisner
R
R
D000818:Animals; D001692:Biological Transport; D015820:Cadherins / Q000378:metabolism; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D008321:Mammary Glands, Animal / Q000166:cytology; D008648:Mesoderm; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D051176:beta Catenin; D000095002:Delta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse