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dc.contributor.authorSoady, KJ
dc.contributor.authorTornillo, G
dc.contributor.authorKendrick, H
dc.contributor.authorMeniel, V
dc.contributor.authorOlijnyk-Dallis, D
dc.contributor.authorMorris, JS
dc.contributor.authorStein, T
dc.contributor.authorGusterson, BA
dc.contributor.authorIsacke, CM
dc.contributor.authorSmalley, MJ
dc.date.accessioned2017-09-26T14:38:39Z
dc.date.issued2017-10
dc.identifier.citationDevelopment (Cambridge, England), 2017, 144 (20), pp. 3777 - 3788
dc.identifier.issn0950-1991
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/843
dc.identifier.eissn1477-9129
dc.identifier.doi10.1242/dev.149120
dc.description.abstractPTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here, we demonstrate that PTPRB negatively regulates branching morphogenesis in the mouse mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in oestrogen receptor-positive luminal cells. During mammary development, Ptprb expression is downregulated during puberty, a period of extensive ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of fibroblast growth factor receptor (FGFR) activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology.
dc.formatPrint-Electronic
dc.format.extent3777 - 3788
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectMammary Glands, Animal
dc.subjectOrganoids
dc.subjectEpithelial Cells
dc.subjectStem Cells
dc.subjectAnimals
dc.subjectMice
dc.subjectExtracellular Signal-Regulated MAP Kinases
dc.subjectFibroblast Growth Factor 2
dc.subjectGreen Fluorescent Proteins
dc.subjectReceptors, Fibroblast Growth Factor
dc.subjectReceptors, Estrogen
dc.subjectRNA, Small Interfering
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectGene Expression Profiling
dc.subjectSignal Transduction
dc.subjectGene Expression Regulation, Developmental
dc.subjectPhosphorylation
dc.subjectMorphogenesis
dc.subjectBody Patterning
dc.subjectNeovascularization, Physiologic
dc.subjectTransgenes
dc.subjectFemale
dc.subjectReceptor-Like Protein Tyrosine Phosphatases, Class 3
dc.titleThe receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis.
dc.typeJournal Article
dcterms.dateAccepted2017-08-25
rioxxterms.versionofrecord10.1242/dev.149120
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfDevelopment (Cambridge, England)
pubs.issue20
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.publication-statusPublished
pubs.volume144
pubs.embargo.termsNot known
icr.researchteamMolecular Cell Biologyen_US
dc.contributor.icrauthorIsacke, Clareen


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