File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Promoter methylation and differential expression of π-class glutathione S-transferase in endometrial carcinoma

TitlePromoter methylation and differential expression of π-class glutathione S-transferase in endometrial carcinoma
Authors
Issue Date2005
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://jmd.amjpathol.org
Citation
Journal Of Molecular Diagnostics, 2005, v. 7 n. 1, p. 8-16 How to Cite?
Abstractπ-Class glutathione S-transferase (GSTP1), located on chromosome 11q13, codes for a phase II metabolic enzyme that detoxifies reactive electrophilic intermediates. The protein also interacts with steroid hormones in the human body. The role of GSTP1 in endometrial carcinoma has not been reported. In this study, we aimed at determining the expression of GSTP1 in relation to the epigenetic and genetic changes of the gene in endometrial carcinoma. The GSTP1 protein and mRNA expression was assessed by immunohistochemistry on tissue microarray and quantitative real-time reverse transcriptase-polymerase chain reaction, respectively. Its methylation status was studied by methylation-specific polymerase chain reaction and bisulfite sequencing. Possible mutations in coding region of GSTP1 were assessed by cDNA sequencing. Ninety-seven cases of endometrial carcinoma with available tissue blocks and clinical data were studied. Our results showed that 68.0% (66 of 97) of the cases showed reduced protein expression while 64% (16 of 25) showed reduced mRNA expression; 30.9% (30 of 97) of the cases demonstrated methylated alleles in at least one of the six methylation-specific polymerase chain reaction reactions. The methylation status significantly correlated with reduced protein expression (P = 0.008) and reduced mRNA expression (P = 0.003). Methylation at non-CpG sites including CpCpG trinucleotides and CpT dinucleotides were also observed. cDNA sequencing did not reveal genetic alterations in coding region of the gene. The extent of myometrial invasion was found to be significantly correlated with both the methylation status (P = 0.009) and the protein expression (P = 0.036) of the GSTP1 gene. We postulated that hypermethylation of the GSTP1 gene promoter region may act as a dynamic regulation mechanism contributing to reduced GSTP1 expression, which is associated with myometrial invasion potential of the endometrial carcinoma. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.
Persistent Identifierhttp://hdl.handle.net/10722/49381
ISSN
2015 Impact Factor: 5.201
2015 SCImago Journal Rankings: 2.514
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, QKYen_HK
dc.contributor.authorKhoo, USen_HK
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorLi, SSen_HK
dc.contributor.authorChiu, PMen_HK
dc.contributor.authorMan, LSen_HK
dc.contributor.authorIp, PPCen_HK
dc.contributor.authorXue, WCen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2008-06-12T06:40:57Z-
dc.date.available2008-06-12T06:40:57Z-
dc.date.issued2005en_HK
dc.identifier.citationJournal Of Molecular Diagnostics, 2005, v. 7 n. 1, p. 8-16en_HK
dc.identifier.issn1525-1578en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49381-
dc.description.abstractπ-Class glutathione S-transferase (GSTP1), located on chromosome 11q13, codes for a phase II metabolic enzyme that detoxifies reactive electrophilic intermediates. The protein also interacts with steroid hormones in the human body. The role of GSTP1 in endometrial carcinoma has not been reported. In this study, we aimed at determining the expression of GSTP1 in relation to the epigenetic and genetic changes of the gene in endometrial carcinoma. The GSTP1 protein and mRNA expression was assessed by immunohistochemistry on tissue microarray and quantitative real-time reverse transcriptase-polymerase chain reaction, respectively. Its methylation status was studied by methylation-specific polymerase chain reaction and bisulfite sequencing. Possible mutations in coding region of GSTP1 were assessed by cDNA sequencing. Ninety-seven cases of endometrial carcinoma with available tissue blocks and clinical data were studied. Our results showed that 68.0% (66 of 97) of the cases showed reduced protein expression while 64% (16 of 25) showed reduced mRNA expression; 30.9% (30 of 97) of the cases demonstrated methylated alleles in at least one of the six methylation-specific polymerase chain reaction reactions. The methylation status significantly correlated with reduced protein expression (P = 0.008) and reduced mRNA expression (P = 0.003). Methylation at non-CpG sites including CpCpG trinucleotides and CpT dinucleotides were also observed. cDNA sequencing did not reveal genetic alterations in coding region of the gene. The extent of myometrial invasion was found to be significantly correlated with both the methylation status (P = 0.009) and the protein expression (P = 0.036) of the GSTP1 gene. We postulated that hypermethylation of the GSTP1 gene promoter region may act as a dynamic regulation mechanism contributing to reduced GSTP1 expression, which is associated with myometrial invasion potential of the endometrial carcinoma. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://jmd.amjpathol.orgen_HK
dc.relation.ispartofJournal of Molecular Diagnosticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCarcinoma, Endometrioid - enzymology - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshEndometrial Neoplasms - enzymology - geneticsen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGlutathione Transferase - analysis - genetics - metabolismen_HK
dc.titlePromoter methylation and differential expression of π-class glutathione S-transferase in endometrial carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1525-1578&volume=7&issue=1&spage=8&epage=16&date=2005&atitle=Promoter+methylation+and+differential+expression+of+π-class+glutathione+S-transferase+in+endometrial+carcinomaen_HK
dc.identifier.emailKhoo, US: uskhoo@hku.hken_HK
dc.identifier.emailChan, KYK: kelvinc@pathology.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.identifier.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid15681469-
dc.identifier.pmcidPMC1867507en_HK
dc.identifier.scopuseid_2-s2.0-20044396533en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-20044396533&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue1en_HK
dc.identifier.spage8en_HK
dc.identifier.epage16en_HK
dc.identifier.isiWOS:000227823900002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, QKY=8390404100en_HK
dc.identifier.scopusauthoridKhoo, US=7004195799en_HK
dc.identifier.scopusauthoridChan, KYK=7406034195en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridLi, SS=14834253300en_HK
dc.identifier.scopusauthoridChiu, PM=7103182596en_HK
dc.identifier.scopusauthoridMan, LS=8205101800en_HK
dc.identifier.scopusauthoridIp, PPC=7003622683en_HK
dc.identifier.scopusauthoridXue, WC=7103165268en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats