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

Hilmarsdóttir, Bylgja; Briem, Eirikur; Sigurdsson, Valgardur LU ; Franzdóttir, Sigrídur Rut; Ringnér, Markus LU ; Arason, Ari Jon; Bergthorsson, Jon Thor; Magnusson, Magnus Karl and Gudjonsson, Thorarinn (2015) In Developmental Biology 403(2). p.150-161
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Developmental Biology
volume
403
issue
2
pages
150 - 161
publisher
Elsevier
external identifiers
  • pmid:25967125
  • wos:000356839600004
  • scopus:84931573193
ISSN
1095-564X
DOI
10.1016/j.ydbio.2015.05.007
language
English
LU publication?
yes
id
71e2db1d-c153-42f1-b337-c24e01fab311 (old id 5453337)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25967125?dopt=Abstract
date added to LUP
2015-06-03 12:20:02
date last changed
2017-09-10 03:17:15
@article{71e2db1d-c153-42f1-b337-c24e01fab311,
  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       = {Hilmarsdóttir, Bylgja and Briem, Eirikur and Sigurdsson, Valgardur and Franzdóttir, Sigrídur Rut and Ringnér, Markus and Arason, Ari Jon and Bergthorsson, Jon Thor and Magnusson, Magnus Karl and Gudjonsson, Thorarinn},
  issn         = {1095-564X},
  language     = {eng},
  number       = {2},
  pages        = {150--161},
  publisher    = {Elsevier},
  series       = {Developmental Biology},
  title        = {MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.},
  url          = {http://dx.doi.org/10.1016/j.ydbio.2015.05.007},
  volume       = {403},
  year         = {2015},
}