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

Dev Biol 2015 Jul 9;403(2):150-61. Epub 2015 May 9.

Stem Cell Research Unit, Biomedical Center, Department of Anatomy, Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Department of Laboratory Hematology, Landspitali-University Hospital, Iceland. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ydbio.2015.05.007DOI Listing
July 2015
23 Reads

Publication Analysis

Top Keywords

branching morphogenesis
12
luminal- myoepithelial
12
myoepithelial differentiation
12
breast epithelial
12
∆np63 d492m
12
d492m restored
8
luminal myoepithelial
8
expression mir-200c-141
8
mir-200c-141 ∆np63
8
epithelial
7
d492m
7
myoepithelial
6
breast
6
emt
5
d492m resistance
4
suppression mir-200
4
d492m suppression
4
emt conclusion
4
resistance endothelial
4
mir-200 family
4

Similar Publications