Article: EZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-β 1 and is a predictor of outcome in ovarian carcinoma patients

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TitleEZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-β 1 and is a predictor of outcome in ovarian carcinoma patients
AuthorsRao, ZY1
Cai, MY1
Yang, GF1
He, LR1
Mai, SJ1
Hua, WF1
Liao, YJ1
Deng, HX1
Chen, YC2
Guan, XY1
Zeng, YX1
Kung, HF1 2
Xie, D1
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
CitationCarcinogenesis, 2010, v. 31 n. 9, p. 1576-1583 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgq150
AbstractIt was suggested that the enhancer of zeste homolog 2 (EZH2) gene is a putative candidate oncogene in several types of human cancer. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, EZH2 expression was examined by immunohistochemistry (IHC) in cohorts of normal and tumorous ovarian tissues. High expression of EZH2 was examined in none of the normal ovaries, in 3% of the cystadenomas, in 23% of the borderline tumors and in 50% of the ovarian carcinomas, respectively. In the ovarian carcinomas, high expression of EZH2 was positively correlated with an ascending histological grade and/or advanced stage of the disease (P < 0.05). Moreover, high expression of EZH2 in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (P < 0.05). In ovarian carcinoma HO-8910 and UACC-326 cell lines, EZH2 knockdown by RNA interference led to a G 1 phase cell cycle arrest, reduced cell growth/proliferation and inhibited cell migration and/or invasion in vitro. In addition, EZH2 knockdown was found to reduce transforming growth factor-β1 (TGF-β1) expression and increase E-cadherin expression either in the transcript or in the protein levels. Furthermore, a significant positive correlation between overexpression of EZH2 and TGF-β1 in ovarian carcinoma tissues was observed (P < 0.001). These findings suggest a potential important role of EZH2 in the control of cell migration and/or invasion via the regulation of TGF-β1 expression, and the high expression of EZH2, as detected by IHC, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma. © The Author 2010. Published by Oxford University Press. All rights reserved.
ISSN0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
DOIhttp://dx.doi.org/10.1093/carcin/bgq150
ISI Accession Number IDWOS:000281530400010
Funding AgencyGrant Number
Major State Basic Research Program of China2006CB910104
2010CB529401
Nature Science Foundation of China30772334
Funding Information:

Major State Basic Research Program of China (2006CB910104 and 2010CB529401); Nature Science Foundation of China (30772334).

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorRao, ZY
dc.contributor.authorCai, MY
dc.contributor.authorYang, GF
dc.contributor.authorHe, LR
dc.contributor.authorMai, SJ
dc.contributor.authorHua, WF
dc.contributor.authorLiao, YJ
dc.contributor.authorDeng, HX
dc.contributor.authorChen, YC
dc.contributor.authorGuan, XY
dc.contributor.authorZeng, YX
dc.contributor.authorKung, HF
dc.contributor.authorXie, D
dc.date.accessioned2012-06-26T06:11:40Z
dc.date.available2012-06-26T06:11:40Z
dc.date.issued2010
dc.description.abstractIt was suggested that the enhancer of zeste homolog 2 (EZH2) gene is a putative candidate oncogene in several types of human cancer. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, EZH2 expression was examined by immunohistochemistry (IHC) in cohorts of normal and tumorous ovarian tissues. High expression of EZH2 was examined in none of the normal ovaries, in 3% of the cystadenomas, in 23% of the borderline tumors and in 50% of the ovarian carcinomas, respectively. In the ovarian carcinomas, high expression of EZH2 was positively correlated with an ascending histological grade and/or advanced stage of the disease (P < 0.05). Moreover, high expression of EZH2 in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (P < 0.05). In ovarian carcinoma HO-8910 and UACC-326 cell lines, EZH2 knockdown by RNA interference led to a G 1 phase cell cycle arrest, reduced cell growth/proliferation and inhibited cell migration and/or invasion in vitro. In addition, EZH2 knockdown was found to reduce transforming growth factor-β1 (TGF-β1) expression and increase E-cadherin expression either in the transcript or in the protein levels. Furthermore, a significant positive correlation between overexpression of EZH2 and TGF-β1 in ovarian carcinoma tissues was observed (P < 0.001). These findings suggest a potential important role of EZH2 in the control of cell migration and/or invasion via the regulation of TGF-β1 expression, and the high expression of EZH2, as detected by IHC, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma. © The Author 2010. Published by Oxford University Press. All rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCarcinogenesis, 2010, v. 31 n. 9, p. 1576-1583 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgq150
dc.identifier.citeulike7842375
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgq150
dc.identifier.epage1583
dc.identifier.isiWOS:000281530400010
Funding AgencyGrant Number
Major State Basic Research Program of China2006CB910104
2010CB529401
Nature Science Foundation of China30772334
Funding Information:

Major State Basic Research Program of China (2006CB910104 and 2010CB529401); Nature Science Foundation of China (30772334).

dc.identifier.issn0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
dc.identifier.issue9
dc.identifier.pmid20668008
dc.identifier.scopuseid_2-s2.0-77956277833
dc.identifier.spage1576
dc.identifier.urihttp://hdl.handle.net/10722/150831
dc.identifier.volume31
dc.languageeng
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofCarcinogenesis
dc.relation.referencesReferences in Scopus
dc.subject.meshAdenocarcinoma, Mucinous - Genetics - Metabolism - Pathology
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 And Over
dc.subject.meshBlotting, Western
dc.subject.meshCell Adhesion
dc.subject.meshCell Cycle
dc.subject.meshCell Movement
dc.subject.meshCystadenocarcinoma, Serous - Genetics - Metabolism - Pathology
dc.subject.meshDna-Binding Proteins - Physiology
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHumans
dc.subject.meshImmunoenzyme Techniques
dc.subject.meshIn Situ Hybridization, Fluorescence
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Invasiveness
dc.subject.meshNeoplasm Metastasis
dc.subject.meshNeoplasm Staging
dc.subject.meshOvarian Neoplasms - Genetics - Metabolism - Pathology
dc.subject.meshRna, Messenger - Genetics
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSurvival Rate
dc.subject.meshTissue Array Analysis
dc.subject.meshTranscription Factors - Physiology
dc.subject.meshTransforming Growth Factor Beta1 - Genetics - Metabolism
dc.subject.meshTumor Cells, Cultured
dc.subject.meshYoung Adult
dc.titleEZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-β 1 and is a predictor of outcome in ovarian carcinoma patients
dc.typeArticle
Author Affiliations
  1. Sun Yat-Sen University
  2. Chinese University of Hong Kong