Centrosome Aberrations Associated with Cellular Senescence and p53 Localization at Supernumerary Centrosomes英文文献资料.docVIP

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Centrosome Aberrations Associated with Cellular Senescence and p53 Localization at Supernumerary Centrosomes英文文献资料.doc

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Centrosome Aberrations Associated with Cellular Senescence and p53 Localization at Supernumerary Centrosomes英文文献资料

HindawiPublishingCorporation OxidativeMedicineandCellularLongevity Volume2012,ArticleID217594,9pages doi:10.1155/2012/217594 ResearchArticle CentrosomeAberrationsAssociatedwithCellularSenescence andp53LocalizationatSupernumeraryCentrosomes SusumuOhshima DivisionofMorphologicalScience,BiomedicalResearchCenter,SaitamaMedicalUniversity,38Morohongo,Moroyama,Iruma, Saitama350-0495,Japan CorrespondenceshouldbeaddressedtoSusumuOhshima,sohshima@saitama-med.ac.jp Received28May2012;Revised27August2012;Accepted11September2012 AcademicEditor:WilliamC.Burhans Copyright?2012SusumuOhshima.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Centrosomeoverduplicationorampli?cationhasbeenobservedinmanyhumancancersandinpremalignanttissue,butthe mechanisms leading to such centrosome aberrations are not fully understood. We previously showed that abnormal mitotic cells with supernumerary centrosomes increase with replicative senescence in human ?broblasts, especially in a polyploid subpopulation. This study examines localization of p53 protein at centrosomes in mitotic cells, which is often observed in associationwithDNAdamageresponse,toinvestigateapossibleassociationbetweenp53localizationandnumericalcentrosome aberrationsinducedbycellularsenescence.Culturesatlaterpassagesorthe4thdayafterexposuretoH2O2 showedincreased frequenciesofmitoticcellswith supernumerary centrosomes, especiallyinapolyploid subpopulation.Immunohistochemical analysisfrequentlyshowedp53-positivefociinmitoticcells,andsomewerelocalizedatcentrosomes.Thenumberofp53-positive foci in mitotic cells and its localization to centrosomes increased with replicative and premature senescence. Supernumerary centrosomesshowedhigherfrequenciesofp53localizationcomparedtonormallyduplicatedcentrosomes.Centrosome-associated p53 protein was phosphorylated at Ser15. These data suggest a possib