File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Downregulation of ASPP1 in gestational trophoblastic disease: Correlation with hypermethylation, apoptotic activity and clinical outcome

TitleDownregulation of ASPP1 in gestational trophoblastic disease: Correlation with hypermethylation, apoptotic activity and clinical outcome
Authors
Keywordsapoptotic activity
ASPP1
choriocarcinomas
gestational trophoblastic disease
hypermethylation
methylation
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/
Citation
Modern Pathology, 2011, v. 24 n. 4, p. 522-532 How to Cite?
Abstract
Gestational trophoblastic disease encompasses a spectrum of trophoblastic lesions including true neoplasms such as choriocarcinomas and the potentially malignant hydatidiform moles, which may develop persistent disease requiring chemotherapy. ASPP1, a member of apoptosis-stimulating proteins of p53 (ASPPs), is a proapoptotic protein that can stimulate apoptosis through its interaction with p53. We evaluated the promoter methylation and expression profiles of ASPP1 in different trophoblastic tissues and its in vitro functional effect on two choriocarcinoma cell lines, namely JEG-3 and JAR. Significant downregulation of ASPP1 mRNA and protein levels was demonstrated in hydatidiform moles and choriocarcinomas, when compared with normal placentas by quantitative-PCR and immunohistochemistry. The ASPP1 mRNA level was significantly correlated with its hypermethylation status, evaluated with methylation-specific PCR, in placenta and gestational trophoblastic disease samples (P=0.024). Moreover, lower ASPP1 immunoreactivity was shown in hydatidiform moles that progressed to persistent gestational trophoblastic neoplasms than in those that regressed (P=0.045). A significant correlation was also found between expression of ASPP1 and proliferative indices (assessed by Ki67 and MCM7), apoptotic activity (M30 CytoDeath antibody), p53 and caspase-8 immunoreactivities. An in vitro study showed that ectopic expression of ASPP1 could trigger apoptosis through intrinsic and extrinsic pathways as indicated by an increase in cleaved caspase-9 and Fas ligand protein expression. The latter suggests a hitherto unreported novel link between ASPP1 and the extrinsic pathway of apoptosis. Our findings suggest that downregulation of ASPP1 by hypermethylation may be involved in the pathogenesis and progress of gestational trophoblastic disease, probably through its effect on apoptosis. © 2011 USCAP, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/139929
ISSN
2013 Impact Factor: 6.364
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative RegionAoE/M-04/06
Funding Information:

This study was supported by grants from the 'Centre for Research into Circulating Fetal Nucleic Acids' (AoE/M-04/06) funded by the Research Grants Council of the Hong Kong Special Administrative Region.

References

 

DC FieldValueLanguage
dc.contributor.authorMak, VCYen_HK
dc.contributor.authorLee, Len_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorWong, OGWen_HK
dc.contributor.authorLu, Xen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2011-09-23T06:01:43Z-
dc.date.available2011-09-23T06:01:43Z-
dc.date.issued2011en_HK
dc.identifier.citationModern Pathology, 2011, v. 24 n. 4, p. 522-532en_HK
dc.identifier.issn0893-3952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139929-
dc.description.abstractGestational trophoblastic disease encompasses a spectrum of trophoblastic lesions including true neoplasms such as choriocarcinomas and the potentially malignant hydatidiform moles, which may develop persistent disease requiring chemotherapy. ASPP1, a member of apoptosis-stimulating proteins of p53 (ASPPs), is a proapoptotic protein that can stimulate apoptosis through its interaction with p53. We evaluated the promoter methylation and expression profiles of ASPP1 in different trophoblastic tissues and its in vitro functional effect on two choriocarcinoma cell lines, namely JEG-3 and JAR. Significant downregulation of ASPP1 mRNA and protein levels was demonstrated in hydatidiform moles and choriocarcinomas, when compared with normal placentas by quantitative-PCR and immunohistochemistry. The ASPP1 mRNA level was significantly correlated with its hypermethylation status, evaluated with methylation-specific PCR, in placenta and gestational trophoblastic disease samples (P=0.024). Moreover, lower ASPP1 immunoreactivity was shown in hydatidiform moles that progressed to persistent gestational trophoblastic neoplasms than in those that regressed (P=0.045). A significant correlation was also found between expression of ASPP1 and proliferative indices (assessed by Ki67 and MCM7), apoptotic activity (M30 CytoDeath antibody), p53 and caspase-8 immunoreactivities. An in vitro study showed that ectopic expression of ASPP1 could trigger apoptosis through intrinsic and extrinsic pathways as indicated by an increase in cleaved caspase-9 and Fas ligand protein expression. The latter suggests a hitherto unreported novel link between ASPP1 and the extrinsic pathway of apoptosis. Our findings suggest that downregulation of ASPP1 by hypermethylation may be involved in the pathogenesis and progress of gestational trophoblastic disease, probably through its effect on apoptosis. © 2011 USCAP, Inc. All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/modpathol/en_HK
dc.relation.ispartofModern Pathologyen_HK
dc.subjectapoptotic activityen_HK
dc.subjectASPP1en_HK
dc.subjectchoriocarcinomasen_HK
dc.subjectgestational trophoblastic diseaseen_HK
dc.subjecthypermethylationen_HK
dc.subjectmethylationen_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - genetics - metabolism-
dc.subject.meshApoptosis Regulatory Proteins - genetics - metabolism-
dc.subject.meshChoriocarcinoma - genetics - metabolism - pathology-
dc.subject.meshDNA Methylation-
dc.subject.meshHydatidiform Mole - genetics - metabolism - pathology-
dc.titleDownregulation of ASPP1 in gestational trophoblastic disease: Correlation with hypermethylation, apoptotic activity and clinical outcomeen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0893-3952&volume=24&issue=4&spage=522&epage=532&date=2011&atitle=Downregulation+of+ASPP1+in+gestational+trophoblastic+disease:+correlation+with+hypermethylation,+apoptotic+activity+and+clinical+outcome-
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_fulltext-
dc.identifier.doi10.1038/modpathol.2010.216en_HK
dc.identifier.pmid21102414en_HK
dc.identifier.scopuseid_2-s2.0-79953305430en_HK
dc.identifier.hkuros192466en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79953305430&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue4en_HK
dc.identifier.spage522en_HK
dc.identifier.epage532en_HK
dc.identifier.isiWOS:000289072100006-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridMak, VCY=36508943200en_HK
dc.identifier.scopusauthoridLee, L=47161324000en_HK
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridWong, OGW=7004813981en_HK
dc.identifier.scopusauthoridLu, X=26643632100en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.citeulike8335420-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats