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

Författare:
  • Bylgja Hilmarsdóttir
  • Eirikur Briem
  • Valgardur Sigurdsson
  • Sigrídur Rut Franzdóttir
  • Markus Ringnér
  • Ari Jon Arason
  • Jon Thor Bergthorsson
  • Magnus Karl Magnusson
  • Thorarinn Gudjonsson
Publiceringsår: 2015
Språk: Engelska
Sidor: 150-161
Publikation/Tidskrift/Serie: Developmental Biology
Volym: 403
Nummer: 2
Dokumenttyp: Artikel i tidskrift
Förlag: Elsevier

Abstract english

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.

Keywords

  • Cancer and Oncology
  • Hematology

Other

Published
  • ISSN: 1095-564X
Markus Ringnér
E-post: markus [dot] ringner [at] biol [dot] lu [dot] se

Forskningsingenjör

Molekylär cellbiologi

B-A317

Sölvegatan 35, Lund

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