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Article: Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival

TitleOverexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival
Authors
KeywordsDock180 expression
Metastasis
Ovarian cancer
Prognostic factor
Issue Date2011
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/HIS
Citation
Histopathology, 2011, v. 59 n. 6, p. 1163-1172 How to Cite?
Abstract
Aims: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. Methods and results: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n=5) and clinical samples of ovarian borderline tumours (n=21) and invasive cancers (n=108) when compared with ovarian epithelial cell lines (n=3) and benign cystadenomas (n=10) (P<0.05). High Dock180 cytoplasmic expression in ovarian cancer (n=108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P<0.05), as well as poor overall and disease-free survival (P=0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P<0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. Conclusions: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target. © 2011 Blackwell Publishing Limited.
Persistent Identifierhttp://hdl.handle.net/10722/148679
ISSN
2013 Impact Factor: 3.301
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative RegionHKU 7503/06M
Hong Kong Anti-Cancer Society Fund
Funding Information:

The pCAGGS-Dock180 and control vector were kind gifts from Dr Jun-ichi Miyasaki (Osaka University, Osaka, Japan). This study was supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7503/06M) and Hong Kong Anti-Cancer Society Fund.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorZhao, Fen_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorJiang, Len_HK
dc.contributor.authorTam, KFen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorLe, XFen_HK
dc.contributor.authorWong, OGWen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2012-05-29T06:14:37Z-
dc.date.available2012-05-29T06:14:37Z-
dc.date.issued2011en_HK
dc.identifier.citationHistopathology, 2011, v. 59 n. 6, p. 1163-1172en_HK
dc.identifier.issn0309-0167en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148679-
dc.description.abstractAims: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. Methods and results: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n=5) and clinical samples of ovarian borderline tumours (n=21) and invasive cancers (n=108) when compared with ovarian epithelial cell lines (n=3) and benign cystadenomas (n=10) (P<0.05). High Dock180 cytoplasmic expression in ovarian cancer (n=108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P<0.05), as well as poor overall and disease-free survival (P=0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P<0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. Conclusions: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target. © 2011 Blackwell Publishing Limited.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/HISen_HK
dc.relation.ispartofHistopathologyen_HK
dc.subjectDock180 expressionen_HK
dc.subjectMetastasisen_HK
dc.subjectOvarian canceren_HK
dc.subjectPrognostic factoren_HK
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 And Overen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarcinoma - Enzymology - Mortality - Pathologyen_US
dc.subject.meshCell Movement - Geneticsen_US
dc.subject.meshCystadenoma - Enzymology - Mortality - Pathologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMicroscopy, Confocalen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeoplasm Gradingen_US
dc.subject.meshNeoplasm Invasiveness - Genetics - Pathologyen_US
dc.subject.meshOvarian Neoplasms - Enzymology - Mortality - Pathologyen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshPrognosisen_US
dc.subject.meshRna, Small Interferingen_US
dc.subject.meshReal-Time Polymerase Chain Reactionen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Markers, Biological - Analysisen_US
dc.subject.meshUp-Regulationen_US
dc.subject.meshYoung Adulten_US
dc.subject.meshRac Gtp-Binding Proteins - Analysis - Biosynthesisen_US
dc.titleOverexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survivalen_HK
dc.typeArticleen_HK
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authoritySiu, MKY=rp00275en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1365-2559.2011.04045.xen_HK
dc.identifier.pmid22175896en_HK
dc.identifier.scopuseid_2-s2.0-84855926182en_HK
dc.identifier.hkuros211340-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855926182&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1163en_HK
dc.identifier.epage1172en_HK
dc.identifier.isiWOS:000298358000014-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease-
dc.identifier.scopusauthoridZhao, F=54897137800en_HK
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridJiang, L=36801738800en_HK
dc.identifier.scopusauthoridTam, KF=35622901400en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridLe, XF=16637748300en_HK
dc.identifier.scopusauthoridWong, OGW=7004813981en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridChan, HY=26024081600en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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