CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells
| Autor: | Yuka Miura, Yohei Hirai, Derek C. Radisky, Natsumi Hagiwara |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Gene isoform
Epithelial-Mesenchymal Transition Morphogenesis Gene Expression Biology Basement Membrane Cell Line Mice Tissue culture Mammary Glands Animal Transforming Growth Factor beta Keratin Gene expression Animals Protein Isoforms Epithelial–mesenchymal transition chemistry.chemical_classification Matrigel Membrane Glycoproteins Cell growth CCAAT-Enhancer-Binding Protein-beta Epithelial Cells Cell Biology Cell biology Drug Combinations chemistry Immunology Female Proteoglycans Collagen Laminin |
| Zdroj: | Experimental Cell Research. 327:146-155 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2014.05.019 |
| Popis: | Activation of the epithelial-mesenchymal transition (EMT) program promotes cell invasion and metastasis, and is reversed through mesenchymal-epithelial transition (MET) after formation of distant metastases. Here, we show that an imbalance of gene products encoded by the transcriptional factor C/EBPβ, LAP (liver-enriched activating protein) and LIP (liver-enriched inhibitory protein), can regulate both EMT- and MET-like phenotypic changes in mouse mammary epithelial cells. By using tetracycline repressive LIP expression constructs, we found that SCp2 cells, a clonal epithelial line of COMMA1-D cells, expressed EMT markers, lost the ability to undergo alveolar-like morphogenesis in 3D Matrigel, and acquired properties of benign adenoma cells. Conversely, we found that inducible expression of LAP in SCg6 cells, a clonal fibroblastic line of COMMA1-D cells, began to express epithelial keratins with suppression of proliferation. The overexpression of the C/EBPβ gene products in these COMMA1-D derivatives was suppressed by long-term cultivation on tissue culture plastic, but gene expression was maintained in cells grown on Matrigel or exposed to proteasome inhibitors. Thus, imbalances of C/EBPβ gene products in mouse mammary epithelial cells, which are affected by contact with basement membrane, are defined as a potential regulator of metastatic potential. |
| Databáze: | OpenAIRE |
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