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Article: Overexpression of NANOG in gestational trophoblastic diseases: Effect on apoptosis, cell invasion, and clinical outcome

TitleOverexpression of NANOG in gestational trophoblastic diseases: Effect on apoptosis, cell invasion, and clinical outcome
Authors
Issue Date2008
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
Citation
American Journal Of Pathology, 2008, v. 173 n. 4, p. 1165-1172 How to Cite?
AbstractGestational trophoblastic disease includes choriocarcinoma, a frankly malignant tumor, and hydatidiform mole (HM), which often leads to the development of persistent gestational trophoblastic neoplasia and requires chemotherapy. NANOG is an important transcription factor that is crucial for maintaining embryonic stem cell self-renewal and pluripotency. We postulated that NANOG is involved in the pathogenesis of gestational trophoblastic disease. In this study, significantly higher NANOG mRNA and protein expression levels, by quantitative PCR and immunoblotting, respectively, were demonstrated in HMs, particularly those that developed persistent disease, when compared with normal placentas. In addition, significantly increased nuclear NANOG immunoreactivity was found by immunohistochemistry in HMs (P < 0.001) and choriocarcinoma (P = 0.002). Higher NANOG expression levels were demonstrated in HMs that developed persistent disease, as compared with those that regressed (P = 0.025). Nuclear localization of NANOG was confirmed by confocal microscopy and immunoblotting in choriocarcinoma cell lines. There was a significant inverse correlation between NANOG immunoreactivity and apoptotic index assessed by M30 CytoDeath antibody (P = 0.012). After stable knockdown of NANOG in the choriocarcinoma cell line JEG-3 by an shRNA approach, increased apoptosis was observed in relation to with enhanced caspases and poly(ADP-ribose) polymerase activities. NANOG knockdown was also associated with decreased mobility and invasion of JEG-3 and downregulation of matrix metalloproteases 2 and 9. These findings suggest that NANOG is involved in the pathogenesis and clinical progress of gestational trophoblastic disease, likely through its effect on apoptosis, cell migration, and invasion. Copyright © American Society for Investigative Pathology.
Persistent Identifierhttp://hdl.handle.net/10722/60373
ISSN
2015 Impact Factor: 4.206
2015 SCImago Journal Rankings: 2.653
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Special Administrative RegionHKU 7309/04M
University of Hong Kong
Funding Information:

Supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7309/04M) and the Conference and Research Council grant from the University of Hong Kong.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorHoi, YCen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-05-31T04:09:20Z-
dc.date.available2010-05-31T04:09:20Z-
dc.date.issued2008en_HK
dc.identifier.citationAmerican Journal Of Pathology, 2008, v. 173 n. 4, p. 1165-1172en_HK
dc.identifier.issn0002-9440en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60373-
dc.description.abstractGestational trophoblastic disease includes choriocarcinoma, a frankly malignant tumor, and hydatidiform mole (HM), which often leads to the development of persistent gestational trophoblastic neoplasia and requires chemotherapy. NANOG is an important transcription factor that is crucial for maintaining embryonic stem cell self-renewal and pluripotency. We postulated that NANOG is involved in the pathogenesis of gestational trophoblastic disease. In this study, significantly higher NANOG mRNA and protein expression levels, by quantitative PCR and immunoblotting, respectively, were demonstrated in HMs, particularly those that developed persistent disease, when compared with normal placentas. In addition, significantly increased nuclear NANOG immunoreactivity was found by immunohistochemistry in HMs (P < 0.001) and choriocarcinoma (P = 0.002). Higher NANOG expression levels were demonstrated in HMs that developed persistent disease, as compared with those that regressed (P = 0.025). Nuclear localization of NANOG was confirmed by confocal microscopy and immunoblotting in choriocarcinoma cell lines. There was a significant inverse correlation between NANOG immunoreactivity and apoptotic index assessed by M30 CytoDeath antibody (P = 0.012). After stable knockdown of NANOG in the choriocarcinoma cell line JEG-3 by an shRNA approach, increased apoptosis was observed in relation to with enhanced caspases and poly(ADP-ribose) polymerase activities. NANOG knockdown was also associated with decreased mobility and invasion of JEG-3 and downregulation of matrix metalloproteases 2 and 9. These findings suggest that NANOG is involved in the pathogenesis and clinical progress of gestational trophoblastic disease, likely through its effect on apoptosis, cell migration, and invasion. Copyright © American Society for Investigative Pathology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.orgen_HK
dc.relation.ispartofAmerican Journal of Pathologyen_HK
dc.subject.meshApoptosis-
dc.subject.meshCaspases - metabolism-
dc.subject.meshCell Cycle-
dc.subject.meshGestational Trophoblastic Neoplasms - genetics - pathology - therapy-
dc.subject.meshHomeodomain Proteins - genetics - metabolism-
dc.titleOverexpression of NANOG in gestational trophoblastic diseases: Effect on apoptosis, cell invasion, and clinical outcomeen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9440&volume=173&issue=4&spage=1165&epage=1172&date=2008&atitle=Overexpression+of+NANOG+in+gestational+trophoblastic+diseases:+effect+on+apoptosis,+cell+invasion,+and+clinical+outcomeen_HK
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailChan, KYK: kelvinc@pathology.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.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.2353/ajpath.2008.080288en_HK
dc.identifier.pmid18772339-
dc.identifier.pmcidPMC2543083-
dc.identifier.scopuseid_2-s2.0-53149084888en_HK
dc.identifier.hkuros150696en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-53149084888&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume173en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1165en_HK
dc.identifier.epage1172en_HK
dc.identifier.isiWOS:000259648000024-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectStem cell related genes in gestational trophoblastic diseases-
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridHoi, YC=25122433900en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridChan, KYK=7406034195en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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