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Article: Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma

TitleDownregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma
Authors
KeywordsGastric adenocarcinoma
hMLH1
ID4
Microarray
Promoter methylation
Issue Date2003
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2003, v. 22 n. 44, p. 6946-6953 How to Cite?
AbstractPromoter hypermethylation has become apparent as a common mechanism of gene silencing in cancer. Based on our published microarray expression data, we noticed a prominent downregulation of ID4 in gastric adenocarcinoma. The dense 5′ CpG island covering the previously mapped upstream promoter of ID4 has prompted us to relate its downregulation to promoter hypermethylation. ID proteins are distinct members in the helix-loop-helix family of transcriptional regulators, which modulate various key developmental processes. Emerging data have suggested the involvement of ID genes in tumorigenesis. In this study using bisulfite genomic sequencing, we have found hypermethylation of ID4 promoter in most gastric cancer cell lines and 30% of primary tumors. This correlated with decreased level of ID4 expression. Restoration of ID4 expression in various gastric cancer cell lines was achieved by treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine, which at times required the synergistic action of the histone deacetylase inhibitor trichostatin A, but not with trichostatin A alone. Re-expression was accompanied by the corresponding ID4 promoter demethylation. Furthermore, we have found significant association of ID4 promoter methylation with hMLH1 promoter methylation (P = 0.008) and microsatellite instability (P = 0.006). Overall, our results have shown that transcriptional silencing of ID4 is related to the aberrant methylation of its promoter in gastric cancer. The significant association of ID4 and hMLH1 promoter hypermethylation suggested that ID4 may also be among the genes being targeted in the CpG island methylator phenotype tumorigenic pathway.
Persistent Identifierhttp://hdl.handle.net/10722/88814
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, ASWen_HK
dc.contributor.authorTsui, WYen_HK
dc.contributor.authorChen, Xen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorChan, TLen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorLi, Ren_HK
dc.contributor.authorSo, Sen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorLeung, SYen_HK
dc.date.accessioned2010-09-06T09:48:20Z-
dc.date.available2010-09-06T09:48:20Z-
dc.date.issued2003en_HK
dc.identifier.citationOncogene, 2003, v. 22 n. 44, p. 6946-6953en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88814-
dc.description.abstractPromoter hypermethylation has become apparent as a common mechanism of gene silencing in cancer. Based on our published microarray expression data, we noticed a prominent downregulation of ID4 in gastric adenocarcinoma. The dense 5′ CpG island covering the previously mapped upstream promoter of ID4 has prompted us to relate its downregulation to promoter hypermethylation. ID proteins are distinct members in the helix-loop-helix family of transcriptional regulators, which modulate various key developmental processes. Emerging data have suggested the involvement of ID genes in tumorigenesis. In this study using bisulfite genomic sequencing, we have found hypermethylation of ID4 promoter in most gastric cancer cell lines and 30% of primary tumors. This correlated with decreased level of ID4 expression. Restoration of ID4 expression in various gastric cancer cell lines was achieved by treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine, which at times required the synergistic action of the histone deacetylase inhibitor trichostatin A, but not with trichostatin A alone. Re-expression was accompanied by the corresponding ID4 promoter demethylation. Furthermore, we have found significant association of ID4 promoter methylation with hMLH1 promoter methylation (P = 0.008) and microsatellite instability (P = 0.006). Overall, our results have shown that transcriptional silencing of ID4 is related to the aberrant methylation of its promoter in gastric cancer. The significant association of ID4 and hMLH1 promoter hypermethylation suggested that ID4 may also be among the genes being targeted in the CpG island methylator phenotype tumorigenic pathway.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectGastric adenocarcinomaen_HK
dc.subjecthMLH1en_HK
dc.subjectID4en_HK
dc.subjectMicroarrayen_HK
dc.subjectPromoter methylationen_HK
dc.subject.meshAdenocarcinoma - genetics - metabolismen_HK
dc.subject.meshAzacitidine - analogs & derivatives - therapeutic useen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDNA Modification Methylases - antagonists & inhibitorsen_HK
dc.subject.meshDNA-Binding Proteins - metabolismen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshDrug Synergismen_HK
dc.subject.meshEnzyme Inhibitors - therapeutic useen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshHelix-Loop-Helix Motifsen_HK
dc.subject.meshHistone Deacetylase Inhibitorsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHydroxamic Acids - therapeutic useen_HK
dc.subject.meshInhibitor of Differentiation Proteinsen_HK
dc.subject.meshMicrosatellite Repeats - geneticsen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshStomach Neoplasms - genetics - metabolismen_HK
dc.subject.meshTranscription Factors - metabolismen_HK
dc.titleDownregulation of ID4 by promoter hypermethylation in gastric adenocarcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=22&issue=44&spage=6946&epage=6953&date=2003&atitle=Downregulation+of+ID4+by+promoter+hypermethylation+in+gastric+adenocarcinomaen_HK
dc.identifier.emailChan, ASW: agnes@genome.hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.emailChan, TL: tlchan@hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChan, ASW=rp00288en_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1206799en_HK
dc.identifier.pmid14534543-
dc.identifier.scopuseid_2-s2.0-0242490113en_HK
dc.identifier.hkuros86070en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0242490113&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume22en_HK
dc.identifier.issue44en_HK
dc.identifier.spage6946en_HK
dc.identifier.epage6953en_HK
dc.identifier.isiWOS:000185843400017-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, ASW=37019607500en_HK
dc.identifier.scopusauthoridTsui, WY=7005623159en_HK
dc.identifier.scopusauthoridChen, X=8978110800en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridChan, TL=7402687537en_HK
dc.identifier.scopusauthoridChan, ASY=55246984000en_HK
dc.identifier.scopusauthoridLi, R=7404723086en_HK
dc.identifier.scopusauthoridSo, S=7102397384en_HK
dc.identifier.scopusauthoridYuen, ST=8323342200en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK

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