Impaired Mammary Gland Development in Cyl-1−/− Mice during Pregnancy and Lactation Is Epithelial Cell Autonomous

摘要

AspecificdefectofmicelackingcyclinD1(emCyl-1/emsupminus;/minus;/sup)isimpaireddevelopmentofthemammaryglandduringpregnancy.HereweshowthatwhentissuefromemCyl-1/emsupminus;/minus;/supmammaryglandwastransplantedintoemptymammaryfatpadofwild-typemice,theabnormalphenotypewasmaintained,indicatingthatitisepithelialcellautonomous.Nevertheless,inpregnancytheearlyproliferativeresponse,whichischaracterizedbyextensivesidebranching,stilloccursintheabsenceofcyclinD1.However,theresponseisatypicalduetoamarkedreductionintheformationofaccompanyingalveoli.Thisreductionanddelayinalveolardevelopmentpersiststhroughoutpregnancy.Moreover,althoughprolactinsynthesisandreleaseappeartobenormal,lactogenesisisseverelycompromised.Consistentwiththeappearanceofnumeroussidebranches,progesteronereceptorexpressionwasreadilydetectedinthemammarytissueofpregnantemCyl-1/emsupminus;/minus;/supmice,althoughtherewasasignificantchangeintheratioofthetwo(AandB)receptorisoforms.InemCyl-1/emsupminus;/minus;/supmammaryglandsduringlatepregnancytherewasadecreaseintheabundanceoftotalandphosphorylatedStat5a,aswellasdelayedonsetandsubstantialdiminutionofmilkproteinexpression.Thebiochemicalanalysissuggeststhatthereisacumulativedelayingrowthanddifferentiationofthemammaryglandduringpregnancythatresultsinaseverelycompromisedglandwhen,atparturition,furtherdevelopmentiscurtailedbytheabruptchangeinhormonalmilieu./p/div