Bromodomain-Containing Protein 4 A Dynamic Regulator of Breast Cancer Metastasis through Modulation of the Extracellular Matrix英文文献资料.docVIP

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Bromodomain-Containing Protein 4 A Dynamic Regulator of Breast Cancer Metastasis through Modulation of the Extracellular Matrix英文文献资料.doc

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Bromodomain-Containing Protein 4 A Dynamic Regulator of Breast Cancer Metastasis through Modulation of the Extracellular Matrix英文文献资料

HindawiPublishingCorporation InternationalJournalofBreastCancer Volume2012,ArticleID670632,7pages doi:10.1155/2012/670632 ReviewArticle Bromodomain-ContainingProtein4: ADynamicRegulatorofBreastCancerMetastasis throughModulationoftheExtracellularMatrix JudeAlsarrajandKentW.Hunter LaboratoryofCancerBiologyandGenetics,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,MD20892,USA CorrespondenceshouldbeaddressedtoKentW.Hunter,hunterk@ Received27July2011;Revised16September2011;Accepted17September2011 AcademicEditor:DouglasR.Hurst Copyright?2012J.AlsarrajandK.W.Hunter.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Metastasis is an extremely complex process that accounts for most cancer-related deaths. Malignant primary tumors can be removedsurgically,butthecellsthatmigrate,invade,andproliferateatdistantorgansareoftenthecellsthatprovemostdi?cult totargettherapeutically.Thereisgrowingevidencethathostfactorsoutsideoftheprimarytumorsareofmajorimportancein thedevelopmentofmetastasis.Recently,wehaveshownthatthebromodomain-containingprotein4orbromodomain4(Brd4) functionsasaninheritedsusceptibilitygeneforbreastcancerprogressionandmetastasis.Inthispaper,wewilldiscussthathost geneticbackgroundonwhichatumorarisescansigni?cantlyalterthebiologyofthesubsequentmetastaticdisease,andwewill focusontheroleofBrd4inregulatingmetastasissusceptibility. 1.Introduction andbasementmembranes,intravasationandsurvivalinthe smallbloodvesselsorlymphaticchannels,andcolonization in a distant target organ. These steps are usually followed byextravasationintothesurroundingtissue,survivalinthe foreign microenvironment, proliferation, and induction of angiogenesis(Figure1).Ithasbecomeapparentthatthevast majorityoftumorcellswithintheprimarytumorandalso the disseminated tumor cells will not form distant metas- tases, either because they die or remain dormant [4