MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.

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title = "MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.",
abstract = "The epithelial compartment of the breast contains two lineages, the luminal- and the myoepithelial cells. D492 is a breast epithelial cell line with stem cell properties that forms branching epithelial structures in 3D culture with both luminal- and myoepithelial differentiation. We have recently shown that D492 undergo epithelial to mesenchymal transition (EMT) when co-cultured with endothelial cells. This 3D co-culture model allows critical analysis of breast epithelial lineage development and EMT. In this study, we compared the microRNA (miR) expression profiles for D492 and its mesenchymal-derivative D492M. Suppression of the miR-200 family in D492M was among the most profound changes observed. Exogenous expression of miR-200c-141 in D492M reversed the EMT phenotype resulting in gain of luminal but not myoepithelial differentiation. In contrast, forced expression of ∆Np63 in D492M restored the myoepithelial phenotype only. Co-expression of miR-200c-141 and ∆Np63 in D492M restored the branching morphogenesis in 3D culture underlining the requirement for both luminal and myoepithelial elements for obtaining full branching morphogenesis in breast epithelium. Introduction of a miR-200c-141 construct in both D492 and D492M resulted in resistance to endothelial induced EMT. In conclusion, our data suggests that expression of miR-200c-141 and ∆Np63 in D492M can reverse EMT resulting in luminal- and myoepithelial differentiation, respectively, demonstrating the importance of these molecules in epithelial integrity in the human breast.",
author = "Bylgja Hilmarsd{\'o}ttir and Eirikur Briem and Valgardur Sigurdsson and Franzd{\'o}ttir, {Sigr{\'i}dur Rut} and Markus Ringn{\'e}r and Arason, {Ari Jon} and Bergthorsson, {Jon Thor} and Magnusson, {Magnus Karl} and Thorarinn Gudjonsson",
year = "2015",
doi = "10.1016/j.ydbio.2015.05.007",
language = "English",
volume = "403",
pages = "150--161",
journal = "Developmental Biology",
issn = "1095-564X",
publisher = "Elsevier",
number = "2",