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dc.contributor.authorPihan, German A.
dc.contributor.authorPurohit, Aruna
dc.contributor.authorWallace, Jan
dc.contributor.authorMalhotra, Raji
dc.contributor.authorLiotta, Lance A.
dc.contributor.authorDoxsey, Stephen J.
dc.date2022-08-11T08:09:51.000
dc.date.accessioned2022-08-23T16:46:09Z
dc.date.available2022-08-23T16:46:09Z
dc.date.issued2001-03-31
dc.date.submitted2008-06-18
dc.identifier.citationCancer Res. 2001 Mar 1;61(5):2212-9.
dc.identifier.issn0008-5472 (Print)
dc.identifier.pmid11280789
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40823
dc.description.abstractFactors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11280789&dopt=Abstract">Link to article in PubMed</a>
dc.subjectAntigens
dc.subjectCentrosome
dc.subjectDisease Progression
dc.subjectHumans
dc.subjectMale
dc.subjectPhenotype
dc.subjectProstatic Neoplasms
dc.subjectCell Biology
dc.subjectMedical Cell Biology
dc.subjectMedical Genetics
dc.subjectMedical Molecular Biology
dc.subjectMedical Pathology
dc.subjectOncology
dc.titleCentrosome defects can account for cellular and genetic changes that characterize prostate cancer progression
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume61
dc.source.issue5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1362&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/363
dc.identifier.contextkey533073
refterms.dateFOA2022-08-23T16:46:09Z
html.description.abstract<p>Factors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.</p>
dc.identifier.submissionpathoapubs/363
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Pathology
dc.source.pages2212-9


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