TY - JOUR
T1 - CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells
AU - Miura, Yuka
AU - Hagiwara, Natsumi
AU - Radisky, Derek C.
AU - Hirai, Yohei
N1 - Funding Information:
We thank Dr. Bissell for SCp2 and SCg6 cells and Dr. Takeichi for anti-mouse E- and P-cadherin antibodies. We are grateful to all members of Hirai laboratory for helpful discussions and to Ms. Nakazawa for the technical support. Part of this study was supported by Grant-Aid for Scientific Research (KAKENHI 24590365 ).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2014/9/10
Y1 - 2014/9/10
N2 - 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.
AB - 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.
KW - Basement membrane
KW - C/EBPβ
KW - EMT
KW - Epimorphin
KW - MET
KW - Mammary epithelia
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U2 - 10.1016/j.yexcr.2014.05.019
DO - 10.1016/j.yexcr.2014.05.019
M3 - Article
C2 - 24881817
AN - SCOPUS:84906938853
SN - 0014-4827
VL - 327
SP - 146
EP - 155
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -