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Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492

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dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor University of Iceland
dc.contributor.author Sigurdardottir, Anna Karen
dc.contributor.author Jonasdottir, Arna Steinunn
dc.contributor.author Asbjarnarson, Arni
dc.contributor.author Helgudottir, Hildur Run
dc.contributor.author Gudjonsson, Thorarinn
dc.contributor.author Traustadottir, Gunnhildur Asta
dc.date.accessioned 2022-04-26T01:03:46Z
dc.date.available 2022-04-26T01:03:46Z
dc.date.issued 2021-12
dc.identifier.citation Sigurdardottir , A K , Jonasdottir , A S , Asbjarnarson , A , Helgudottir , H R , Gudjonsson , T & Traustadottir , G A 2021 , ' Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492 ' , Journal of Mammary Gland Biology and Neoplasia , pp. 321-338 . https://doi.org/10.1007/s10911-021-09507-1
dc.identifier.issn 1083-3021
dc.identifier.other PURE: 44748409
dc.identifier.other PURE UUID: fbc8c5f0-7fb4-47fd-851d-32e9fd7b2904
dc.identifier.other Scopus: 85121763479
dc.identifier.uri https://hdl.handle.net/20.500.11815/3079
dc.description Publisher Copyright: © 2021, The Author(s).
dc.description.abstract The human breast is composed of terminal duct lobular units (TDLUs) that are surrounded by stroma. In the TDLUs, basement membrane separates the stroma from the epithelial compartment, which is divided into an inner layer of luminal epithelial cells and an outer layer of myoepithelial cells. Stem cells and progenitor cells also reside within the epithelium and drive a continuous cycle of gland remodelling that occurs throughout the reproductive period. D492 is an epithelial cell line originally isolated from the stem cell population of the breast and generates both luminal and myoepithelial cells in culture. When D492 cells are embedded into 3D reconstituted basement membrane matrix (3D-rBM) they form branching colonies mimicking the TDLUs of the breast, thereby providing a well-suited in vitro model for studies on branching morphogenesis and breast development. Peroxidasin (PXDN) is a heme-containing peroxidase that crosslinks collagen IV with the formation of sulfilimine bonds. Previous studies indicate that PXDN plays an integral role in basement membrane stabilisation by crosslinking collagen IV and as such contributes to epithelial integrity. Although PXDN has been linked to fibrosis and cancer in some organs there is limited information on its role in development, including in the breast. In this study, we demonstrate expression of PXDN in breast epithelium and stroma and apply the D492 cell line to investigate the role of PXDN in cell differentiation and branching morphogenesis in the human breast. Overexpression of PXDN induced basal phenotype in D492 cells, loss of plasticity and inhibition of epithelial-to-mesenchymal transition as is displayed by complete inhibition of branching morphogenesis in 3D culture. This is supported by results from RNA-sequencing which show significant enrichment in genes involved in epithelial differentiation along with significant negative enrichment of EMT factors. Taken together, we provide evidence for a novel role of PXDN in breast epithelial differentiation and mammary gland development.
dc.format.extent 18
dc.format.extent 321-338
dc.language.iso en
dc.relation.ispartofseries Journal of Mammary Gland Biology and Neoplasia; ()
dc.rights info:eu-repo/semantics/openAccess
dc.subject Náttúrufræðingar
dc.subject Branching morphogenesis
dc.subject D492
dc.subject Mammary gland
dc.subject Mammary stem cells
dc.subject p63
dc.subject Peroxidasin
dc.subject Oncology
dc.subject Cancer Research
dc.title Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1007/s10911-021-09507-1
dc.relation.url http://www.scopus.com/inward/record.url?scp=85121763479&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine
dc.contributor.department Clinical Laboratory Services, Diagnostics and Blood Bank

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