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Article: HDPR1, a novel inhibitor of the WNT/β-catenin signaling, is frequently downregulated in hepatocellular carcinoma: Involvement of methylation-mediated gene silencing

TitleHDPR1, a novel inhibitor of the WNT/β-catenin signaling, is frequently downregulated in hepatocellular carcinoma: Involvement of methylation-mediated gene silencing
Authors
Keywordsβ-catenin
Dapper
HDPR1
JNK signaling
WNT/β-catenin signaling
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2005, v. 24 n. 9, p. 1607-1614 How to Cite?
AbstractOncogenic activation of the WNT/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). Dishevelled (DvI), a key activator of the pathway, inhibits the adenomatous polyposis coli complex, and this leads to the accumulation of β-catenin and promotes tumorigenesis. Recently, a novel inhibitor of Dishevelled, namely Dapper (Dpr), was isolated in Xenopus. To explore whether HDPR1, the human homologue of Dpr, has an anti-oncogenic role in hepatocarcinogenesis, we studied the expression of this gene in HCCs. We found that there were two alternatively spliced transcripts of HDPR1, designated as α and β forms, in human liver. Downregulation of the gene expression was observed in 31 (43%) of the 72 human HCC samples using the primer pair that amplified both transcripts. Furthermore, the HDPR1α was down-regulated in 42 (58%) of 72 human HCCs and the downregulation significantly correlated with accumulation of β-catenin. Also, downregulation of HDPR1 by RNA interference in HLE cells led to cytoplasmic accumulation of β-catenin. Furthermore, a CpG island located at the promoter region and exon 1 of the HDPR1 gene was methylated in 22 (51%) of human HCCs. We showed that downregulation of HDPR1, in hepatoma cell lines, was associated with methylation of this CpG island using bisulfite sequencing and 5-aza-2′-deoxycytidine demethylation experiment. In addition to methylation-mediated downregulation of HDPR1, allelic loss (13-28% of informative cases) was detected using microsatellite markers flanking the HDPR1 locus. To conclude, down-regulation of HDPR1 is common in HCCs, frequently involves hypermethylation of the promoter region, and allelic loss of the HDPR1 locus may also play a role. © 2005 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/148395
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYau, TOen_US
dc.contributor.authorChan, CYen_US
dc.contributor.authorChan, KLen_US
dc.contributor.authorLee, MFen_US
dc.contributor.authorWong, CMen_US
dc.contributor.authorFan, STen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2012-05-29T06:12:42Z-
dc.date.available2012-05-29T06:12:42Z-
dc.date.issued2005en_US
dc.identifier.citationOncogene, 2005, v. 24 n. 9, p. 1607-1614en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/148395-
dc.description.abstractOncogenic activation of the WNT/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). Dishevelled (DvI), a key activator of the pathway, inhibits the adenomatous polyposis coli complex, and this leads to the accumulation of β-catenin and promotes tumorigenesis. Recently, a novel inhibitor of Dishevelled, namely Dapper (Dpr), was isolated in Xenopus. To explore whether HDPR1, the human homologue of Dpr, has an anti-oncogenic role in hepatocarcinogenesis, we studied the expression of this gene in HCCs. We found that there were two alternatively spliced transcripts of HDPR1, designated as α and β forms, in human liver. Downregulation of the gene expression was observed in 31 (43%) of the 72 human HCC samples using the primer pair that amplified both transcripts. Furthermore, the HDPR1α was down-regulated in 42 (58%) of 72 human HCCs and the downregulation significantly correlated with accumulation of β-catenin. Also, downregulation of HDPR1 by RNA interference in HLE cells led to cytoplasmic accumulation of β-catenin. Furthermore, a CpG island located at the promoter region and exon 1 of the HDPR1 gene was methylated in 22 (51%) of human HCCs. We showed that downregulation of HDPR1, in hepatoma cell lines, was associated with methylation of this CpG island using bisulfite sequencing and 5-aza-2′-deoxycytidine demethylation experiment. In addition to methylation-mediated downregulation of HDPR1, allelic loss (13-28% of informative cases) was detected using microsatellite markers flanking the HDPR1 locus. To conclude, down-regulation of HDPR1 is common in HCCs, frequently involves hypermethylation of the promoter region, and allelic loss of the HDPR1 locus may also play a role. © 2005 Nature Publishing Group All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subjectβ-catenin-
dc.subjectDapper-
dc.subjectHDPR1-
dc.subjectJNK signaling-
dc.subjectWNT/β-catenin signaling-
dc.subject.meshAdaptor Proteins, Signal Transducingen_US
dc.subject.meshAlternative Splicingen_US
dc.subject.meshCarcinoma, Hepatocellular - Genetics - Pathologyen_US
dc.subject.meshCytoskeletal Proteins - Antagonists & Inhibitorsen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshHumansen_US
dc.subject.meshIntercellular Signaling Peptides And Proteins - Physiologyen_US
dc.subject.meshLiver Neoplasms - Genetics - Pathologyen_US
dc.subject.meshNuclear Proteins - Genetics - Physiologyen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshProtein-Tyrosine Kinases - Antagonists & Inhibitorsen_US
dc.subject.meshRna, Neoplasm - Geneticsen_US
dc.subject.meshSignal Transduction - Physiologyen_US
dc.subject.meshTrans-Activators - Antagonists & Inhibitorsen_US
dc.subject.meshWnt Proteinsen_US
dc.subject.meshBeta Cateninen_US
dc.titleHDPR1, a novel inhibitor of the WNT/β-catenin signaling, is frequently downregulated in hepatocellular carcinoma: Involvement of methylation-mediated gene silencingen_US
dc.typeArticleen_US
dc.identifier.emailWong, CM:jackwong@pathology.hku.hken_US
dc.identifier.emailFan, ST:stfan@hku.hken_US
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_US
dc.identifier.authorityWong, CM=rp00231en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.identifier.authorityNg, IOL=rp00335en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.onc.1208340en_US
dc.identifier.pmid15580286en_US
dc.identifier.scopuseid_2-s2.0-14944353116en_US
dc.identifier.hkuros99511-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-14944353116&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume24en_US
dc.identifier.issue9en_US
dc.identifier.spage1607en_US
dc.identifier.epage1614en_US
dc.identifier.isiWOS:000227218200014-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYau, TO=7006540669-
dc.identifier.scopusauthoridChan, CY=8277448300-
dc.identifier.scopusauthoridChan, KL=8277448400-
dc.identifier.scopusauthoridLee, MF=8277448500-
dc.identifier.scopusauthoridWong, CM=16314668400-
dc.identifier.scopusauthoridFan, ST=7402678224-
dc.identifier.scopusauthoridNg, IOL=7102753722-
dc.identifier.citeulike2169-

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