Quantification of Epithelial Cell Differentiation in Mammary Glands and Carcinomas from DMBA- and MNU-Exposed Rats 英文参考文献.docVIP

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Quantification of Epithelial Cell Differentiation in Mammary Glands and Carcinomas from DMBA- and MNU-Exposed Rats 英文参考文献.doc

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Quantification of Epithelial Cell Differentiation in Mammary Glands and Carcinomas from DMBA- and MNU-Exposed Rats 英文参考文献

QuantificationofEpithelialCellDifferentiationin MammaryGlandsandCarcinomasfromDMBA-and MNU-ExposedRats DeepakSharma.,BartM.G.Smits*.,MarkR.Eichelberg,AmandaL.Meilahn,MatthewJ.Muelbl,JillD. Haag,MichaelN.Gould McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison,Wisconsin,UnitedStatesofAmerica Abstract Ratmammarycarcinogenesismodelshavebeenusedextensivelytostudybreastcancerinitiation,progression,prevention, and intervention. Nevertheless, quantitative molecular data on epithelial cell differentiation in mammary glands of untreated andcarcinogen-exposed ratsis limited.Here, wedescribe thecharacterizationof ratmammary epithelialcells (RMECs)bymulticolorflowcytometryusingantibodiesagainstcellsurfaceproteinsCD24,CD29,CD31,CD45,CD49f,CD61, Peanut Lectin, and Thy-1, intracellular proteins CK14, CK19, and FAK, along with phalloidin and Hoechst staining. We identified the luminal and basal/myoepithelial populations and actively dividing RMECs. In inbred rats susceptible to mammary carcinoma development, we quantified the changes in differentiation of the RMEC populations at 1, 2, and 4 weeksafterexposuretomammarycarcinogensDMBAandMNU.DMBAexposuredidnotalterthepercentageofbasalor luminalcells,butupregulatedCD49f(Integrina6)expressionandincreasedcellcycleactivity.MNUexposureresultedina temporary disruption of the luminal/basal ratio and no CD49f upregulation. When comparing DMBA- or MNU-induced mammary carcinomas, the RMEC differentiation profiles are indistinguishable. The carcinomas compared with mammary glandsfromuntreatedrats,showedupregulationofCD29(Integrinb1)andCD49fexpression,increasedFAK(focaladhesion kinase)activationespecially intheCD29hipopulation,anddecreasedCD61(Integrin b3)expression. Thisstudyprovides quantitativeinsightintotheproteinexpressionphenotypesunderlyingRMECdifferentiation.Theresultshighlightdistinct RMEC differentiation etiologies