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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5453337
- author
- 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
- organization
- publishing date
- 2015
- 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
- pmid:25967125
- 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
- 2016-04-01 10:36:07
- date last changed
- 2022-04-12 07:51:54
@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}},
doi = {{10.1016/j.ydbio.2015.05.007}},
volume = {{403}},
year = {{2015}},
}