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Article: Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival
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TitleOverexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival
 
AuthorsZhao, F1
Siu, MKY1
Jiang, L1
Tam, KF1
Ngan, HYS1
Le, XF2
Wong, OGW1
Wong, ESY1
Chan, HY1
Cheung, ANY1
 
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
 
CitationHistopathology, 2011, v. 59 n. 6, p. 1163-1172 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1365-2559.2011.04045.x
 
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.
 
ISSN0309-0167
2013 Impact Factor: 3.301
 
DOIhttp://dx.doi.org/10.1111/j.1365-2559.2011.04045.x
 
ISI Accession Number IDWOS:000298358000014
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.

 
ReferencesReferences in Scopus
 
GrantsAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
DC FieldValue
dc.contributor.authorZhao, F
 
dc.contributor.authorSiu, MKY
 
dc.contributor.authorJiang, L
 
dc.contributor.authorTam, KF
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorLe, XF
 
dc.contributor.authorWong, OGW
 
dc.contributor.authorWong, ESY
 
dc.contributor.authorChan, HY
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2012-05-29T06:14:37Z
 
dc.date.available2012-05-29T06:14:37Z
 
dc.date.issued2011
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationHistopathology, 2011, v. 59 n. 6, p. 1163-1172 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1365-2559.2011.04045.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1365-2559.2011.04045.x
 
dc.identifier.epage1172
 
dc.identifier.hkuros211340
 
dc.identifier.isiWOS:000298358000014
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.

 
dc.identifier.issn0309-0167
2013 Impact Factor: 3.301
 
dc.identifier.issue6
 
dc.identifier.pmid22175896
 
dc.identifier.scopuseid_2-s2.0-84855926182
 
dc.identifier.spage1163
 
dc.identifier.urihttp://hdl.handle.net/10722/148679
 
dc.identifier.volume59
 
dc.languageeng
 
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/HIS
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofHistopathology
 
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdult
 
dc.subject.meshAged
 
dc.subject.meshAged, 80 And Over
 
dc.subject.meshBlotting, Western
 
dc.subject.meshCarcinoma - Enzymology - Mortality - Pathology
 
dc.subject.meshCell Movement - Genetics
 
dc.subject.meshCystadenoma - Enzymology - Mortality - Pathology
 
dc.subject.meshFemale
 
dc.subject.meshHumans
 
dc.subject.meshImmunohistochemistry
 
dc.subject.meshMicroscopy, Confocal
 
dc.subject.meshMiddle Aged
 
dc.subject.meshNeoplasm Grading
 
dc.subject.meshNeoplasm Invasiveness - Genetics - Pathology
 
dc.subject.meshOvarian Neoplasms - Enzymology - Mortality - Pathology
 
dc.subject.meshPhenotype
 
dc.subject.meshPrognosis
 
dc.subject.meshRna, Small Interfering
 
dc.subject.meshReal-Time Polymerase Chain Reaction
 
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
 
dc.subject.meshTransfection
 
dc.subject.meshTumor Markers, Biological - Analysis
 
dc.subject.meshUp-Regulation
 
dc.subject.meshYoung Adult
 
dc.subject.meshRac Gtp-Binding Proteins - Analysis - Biosynthesis
 
dc.subjectDock180 expression
 
dc.subjectMetastasis
 
dc.subjectOvarian cancer
 
dc.subjectPrognostic factor
 
dc.titleOverexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. University of Texas M. D. Anderson Cancer Center