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Article: Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells

TitleSignificance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells
Authors
Issue Date2002
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2002, v. 62 n. 6, p. 1662-1668 How to Cite?
AbstractChromosome instability is a commonly observed feature in ovarian carcinoma. Mitotic checkpoint controls are thought to be essential for accurate chromosomal segregation, and MAD2 is a key component of this checkpoint. In this study, we investigated the competence of the mitotic checkpoint and its relationship to the expression of MAD2 protein in seven ovarian cancer cell lines. We found that a significant number (43%, three of seven cell lines) of the tested ovarian cancer cells failed to arrest in the G2-M phase of the cell cycle in response to microtubule disruption. This loss of mitotic checkpoint control was associated with reduced expression of the MAD2 protein. To additionally understand the significance of the MAD2 to mitotic checkpoint control, we established an inducible expression system in which MAD2 was induced by the addition of ponasterone A. Notably, the induced expression of MAD2 in two checkpoint-defective ovarian cancer cell lines led to the restoration of mitotic checkpoint response to spindle-disrupting agents. Taken together, our findings suggest that the steady-state amount of MAD2 inside cells may represent a molecular switch for mitotic checkpoint control. This provides a novel insight into the molecular basis of CIN in ovarian carcinoma and has implications for effective use of checkpoint-targeting drugs.
Persistent Identifierhttp://hdl.handle.net/10722/67892
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References
Errata

 

DC FieldValueLanguage
dc.contributor.authorWang, Xen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorNg, RWMen_HK
dc.contributor.authorFeng, Hen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorCheung, ALMen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-09-06T05:59:13Z-
dc.date.available2010-09-06T05:59:13Z-
dc.date.issued2002en_HK
dc.identifier.citationCancer Research, 2002, v. 62 n. 6, p. 1662-1668en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67892-
dc.description.abstractChromosome instability is a commonly observed feature in ovarian carcinoma. Mitotic checkpoint controls are thought to be essential for accurate chromosomal segregation, and MAD2 is a key component of this checkpoint. In this study, we investigated the competence of the mitotic checkpoint and its relationship to the expression of MAD2 protein in seven ovarian cancer cell lines. We found that a significant number (43%, three of seven cell lines) of the tested ovarian cancer cells failed to arrest in the G2-M phase of the cell cycle in response to microtubule disruption. This loss of mitotic checkpoint control was associated with reduced expression of the MAD2 protein. To additionally understand the significance of the MAD2 to mitotic checkpoint control, we established an inducible expression system in which MAD2 was induced by the addition of ponasterone A. Notably, the induced expression of MAD2 in two checkpoint-defective ovarian cancer cell lines led to the restoration of mitotic checkpoint response to spindle-disrupting agents. Taken together, our findings suggest that the steady-state amount of MAD2 inside cells may represent a molecular switch for mitotic checkpoint control. This provides a novel insight into the molecular basis of CIN in ovarian carcinoma and has implications for effective use of checkpoint-targeting drugs.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshCalcium-Binding Proteins - biosynthesis - geneticsen_HK
dc.subject.meshCell Cycle - physiologyen_HK
dc.subject.meshCell Cycle Proteinsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMitosis - physiologyen_HK
dc.subject.meshOvarian Neoplasms - genetics - metabolism - pathologyen_HK
dc.subject.meshPlasmids - geneticsen_HK
dc.subject.meshRepressor Proteinsen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.titleSignificance of MAD2 expression to mitotic checkpoint control in ovarian cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=62&spage=1662&epage=1668&date=2002&atitle=Significance+of+MAD2+expression+to+mitotic+checkpoint+control+in+ovarian+cancer+cellsen_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.emailCheung, ALM:lmcheung@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid11912137-
dc.identifier.scopuseid_2-s2.0-0037085936en_HK
dc.identifier.hkuros69706en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037085936&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume62en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1662en_HK
dc.identifier.epage1668en_HK
dc.identifier.isiWOS:000174560200014-
dc.publisher.placeUnited Statesen_HK
dc.relation.erratumdoi:10.1158/0008-5472.CAN-655COR-
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridNg, RWM=7102153861en_HK
dc.identifier.scopusauthoridFeng, H=7401736336en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK

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