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

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MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis. / Hilmarsdóttir, Bylgja; Briem, Eirikur; Sigurdsson, Valgardur; Franzdóttir, Sigrídur Rut; Ringnér, Markus; Arason, Ari Jon; Bergthorsson, Jon Thor; Magnusson, Magnus Karl; Gudjonsson, Thorarinn.

In: Developmental Biology, Vol. 403, No. 2, 2015, p. 150-161.

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Harvard

Hilmarsdóttir, B, Briem, E, Sigurdsson, V, Franzdóttir, SR, Ringnér, M, Arason, AJ, Bergthorsson, JT, Magnusson, MK & Gudjonsson, T 2015, 'MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.', Developmental Biology, vol. 403, no. 2, pp. 150-161. https://doi.org/10.1016/j.ydbio.2015.05.007

APA

Hilmarsdóttir, B., Briem, E., Sigurdsson, V., Franzdóttir, S. R., Ringnér, M., Arason, A. J., Bergthorsson, J. T., Magnusson, M. K., & Gudjonsson, T. (2015). MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis. Developmental Biology, 403(2), 150-161. https://doi.org/10.1016/j.ydbio.2015.05.007

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Hilmarsdóttir, Bylgja ; Briem, Eirikur ; Sigurdsson, Valgardur ; Franzdóttir, Sigrídur Rut ; Ringnér, Markus ; Arason, Ari Jon ; Bergthorsson, Jon Thor ; Magnusson, Magnus Karl ; Gudjonsson, Thorarinn. / MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis. In: Developmental Biology. 2015 ; Vol. 403, No. 2. pp. 150-161.

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TY - JOUR

T1 - MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.

AU - Hilmarsdóttir, Bylgja

AU - Briem, Eirikur

AU - Sigurdsson, Valgardur

AU - Franzdóttir, Sigrídur Rut

AU - Ringnér, Markus

AU - Arason, Ari Jon

AU - Bergthorsson, Jon Thor

AU - Magnusson, Magnus Karl

AU - Gudjonsson, Thorarinn

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.ydbio.2015.05.007

DO - 10.1016/j.ydbio.2015.05.007

M3 - Article

C2 - 25967125

VL - 403

SP - 150

EP - 161

JO - Developmental Biology

JF - Developmental Biology

SN - 1095-564X

IS - 2

ER -