Title |
MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis
|
---|---|
Published in |
Developmental Biology, May 2015
|
DOI | 10.1016/j.ydbio.2015.05.007 |
Pubmed ID | |
Authors |
Bylgja Hilmarsdóttir, Eirikur Briem, Valgardur Sigurdsson, Sigrídur Rut Franzdóttir, Markus Ringnér, Ari Jon Arason, Jon Thor Bergthorsson, Magnus Karl Magnusson, Thorarinn Gudjonsson |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 34 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 7 | 21% |
Student > Master | 6 | 18% |
Student > Ph. D. Student | 5 | 15% |
Student > Bachelor | 4 | 12% |
Professor > Associate Professor | 4 | 12% |
Other | 5 | 15% |
Unknown | 3 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 12 | 35% |
Agricultural and Biological Sciences | 10 | 29% |
Medicine and Dentistry | 7 | 21% |
Immunology and Microbiology | 1 | 3% |
Neuroscience | 1 | 3% |
Other | 0 | 0% |
Unknown | 3 | 9% |