Signalling Pathways Implicated in Early Mammary Gland Morphogenesis and Breast Cancer 英文参考文献.docVIP

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Signalling Pathways Implicated in Early Mammary Gland Morphogenesis and Breast Cancer 英文参考文献.doc

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Signalling Pathways Implicated in Early Mammary Gland Morphogenesis and Breast Cancer 英文参考文献

Review SignallingPathwaysImplicatedinEarly MammaryGlandMorphogenesisandBreast Cancer Beatrice Howard*, Alan Ashworth ABSTRACT MouseMammaryAnlageDevelopment S Mousemammaryepithelialbudsnormallyformatdistinct positionsalongthebodyaxisandareeasilyvisualisedby stainingforexpressionofmammarybudmarkerssuchasLef1, adownstreamWntsignallingcomponent,orbylight peci?cationofmammaryepithelialcellfateoccurs duringembryogenesisascellsaggregatetoformthe mammaryanlage.Withintheembryonicmammary bud,apopulationofepithelialcellsexiststhatwill subsequentlyproliferatetoformaductaltree?llingthe stromalcompartment,andwhichcanproducemilkupon terminaldifferentiationafterbirth.Subsequently,these structurescanberemodelledandreturnedtoabasalstate afterweaningbeforeregeneratinginfuturepregnancies.The plasticityofthemammaryepithelialcell,andits responsivenesstohormonereceptors,facilitatesthisamazing biologicalfeat,butaberrantsignallingmayalsoresultin unintendedconsequencesintheformoffrequent malignancies.Re?ectingthisintimateconnection,a considerablenumberofsignallingpathwayshavebeen implicatedinbothmammaryglandmorphogenesisand carcinogenesis. microscopicanalysisatE12.5.Histologicalanalysisofsagittal sectionsrevealsthe?rstappearanceofthemousemammary anlageinlateE10/earlyE11embryos[6](Figure1A).Atthis time,distinctellipticalaggregatesofepithelialcellsarevisible atthefuturesiteofmammarybuds3and4asdeterminedby theirpositionsrelativetothesomites(Figure1B).However, scanningelectronmicroscopyrevealsnoovertindicationof mammaryanlageformation[14]atthisstage.ByE11.5(;48 somitestage),anlage3protrudesandisobservedbyscanning electronmicroscopyasaslightelevationabovetheepidermal surface[15].Thisisthe?rstmammaryanlagenpairdetectable atthewholeembryolevel,withanlagen4becomingapparent shortlyafteranlagen3.Pseudostrati?edepitheliumisvisible whencrosssectionsthroughthefuturesiteofbud3are analysedatsimilarstages[6,16].Sincelittlelocalised Introduction proliferationoccursinthepresumptivemammaryregion,itis assumed