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Article: Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation

TitleFunctional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation
Authors
KeywordsCarcinoma
Epigenetic
Methylation
Promoter
Protocadherin
Tumor suppressor gene
Issue Date2006
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2006, v. 25 n. 7, p. 1070-1080 How to Cite?
AbstractProtocadherins constitute the largest subgroup in the cadherin superfamily of cell adhesion molecules. Their major functions are poorly understood, although some are implicated in nervous system development. As tumor-specific promoter methylation is a marker for tumor suppressor genes (TSG), we searched for epigenetically inactivated TSGs using methylation-subtraction combined with pharmacologic demethylation, and identified the PCDH10 CpG island as a methylated sequence in nasopharyngeal carcinoma (NPC). PCDH10 is broadly expressed in all normal adult and fetal tissues including the epithelia, though at different levels. It resides at 4q28.3 - a region with hemizygous deletion detected by array-CGH in NPC cell lines; however, PCDH10 itself is not located within the deletion. In contrast, its transcriptional silencing and promoter methylation were frequently detected in multiple carcinoma cell lines in a biallelic way, including 12/12 nasopharyngeal, 13/16 esophageal, 3/4 breast, 5/5 colorectal, 3/4 cervical, 2/5 lung and 2/8 hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell line. Aberrant methylation was further frequently detected in multiple primary carcinomas (82% in NPC, 42-51% for other carcinomas), but not normal tissues. The transcriptional silencing of PCDH10 could be reversed by pharmacologic demethylation with 5-aza-2′-deoxycytidine or genetic demethylation with double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Ectopic expression of PCDH10 strongly suppressed tumor cell growth, migration, invasion and colony formation. Although the epigenetic and genetic disruptions of several classical cadherins as TSGs have been well documented in tumors, this is the first report that a widely expressed protocadherin can also function as a TSG that is frequently inactivated epigenetically in multiple carcinomas. © 2006 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/67359
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYing, Jen_HK
dc.contributor.authorLi, Hen_HK
dc.contributor.authorSeng, TJen_HK
dc.contributor.authorLangford, Cen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorPutti, Ten_HK
dc.contributor.authorMurray, Pen_HK
dc.contributor.authorChan, ATCen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-09-06T05:54:25Z-
dc.date.available2010-09-06T05:54:25Z-
dc.date.issued2006en_HK
dc.identifier.citationOncogene, 2006, v. 25 n. 7, p. 1070-1080en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67359-
dc.description.abstractProtocadherins constitute the largest subgroup in the cadherin superfamily of cell adhesion molecules. Their major functions are poorly understood, although some are implicated in nervous system development. As tumor-specific promoter methylation is a marker for tumor suppressor genes (TSG), we searched for epigenetically inactivated TSGs using methylation-subtraction combined with pharmacologic demethylation, and identified the PCDH10 CpG island as a methylated sequence in nasopharyngeal carcinoma (NPC). PCDH10 is broadly expressed in all normal adult and fetal tissues including the epithelia, though at different levels. It resides at 4q28.3 - a region with hemizygous deletion detected by array-CGH in NPC cell lines; however, PCDH10 itself is not located within the deletion. In contrast, its transcriptional silencing and promoter methylation were frequently detected in multiple carcinoma cell lines in a biallelic way, including 12/12 nasopharyngeal, 13/16 esophageal, 3/4 breast, 5/5 colorectal, 3/4 cervical, 2/5 lung and 2/8 hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell line. Aberrant methylation was further frequently detected in multiple primary carcinomas (82% in NPC, 42-51% for other carcinomas), but not normal tissues. The transcriptional silencing of PCDH10 could be reversed by pharmacologic demethylation with 5-aza-2′-deoxycytidine or genetic demethylation with double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Ectopic expression of PCDH10 strongly suppressed tumor cell growth, migration, invasion and colony formation. Although the epigenetic and genetic disruptions of several classical cadherins as TSGs have been well documented in tumors, this is the first report that a widely expressed protocadherin can also function as a TSG that is frequently inactivated epigenetically in multiple carcinomas. © 2006 Nature Publishing Group All rights reserved.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.subjectCarcinomaen_HK
dc.subjectEpigeneticen_HK
dc.subjectMethylationen_HK
dc.subjectPromoteren_HK
dc.subjectProtocadherinen_HK
dc.subjectTumor suppressor geneen_HK
dc.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshCadherins - geneticsen_HK
dc.subject.meshCarcinoma - geneticsen_HK
dc.subject.meshCell Movement - geneticsen_HK
dc.subject.meshDNA (Cytosine-5-)-Methyltransferase - antagonists & inhibitorsen_HK
dc.subject.meshDNA Methylation - drug effectsen_HK
dc.subject.meshEpigenesis, Geneticen_HK
dc.subject.meshEsophageal Neoplasms - geneticsen_HK
dc.subject.meshGene Silencing - drug effectsen_HK
dc.subject.meshGenes, Tumor Suppressoren_HK
dc.subject.meshHumansen_HK
dc.subject.meshNasopharyngeal Neoplasms - geneticsen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshSequence Deletionen_HK
dc.subject.meshTranscription, Genetic - geneticsen_HK
dc.titleFunctional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=25&issue=7&spage=1070&epage=80&date=2006&atitle=Functional+epigenetics+identifies+a+protocadherin+PCDH10+as+a+candidate+tumor+suppressor+for+nasopharyngeal,+esophageal+and+multiple+other+carcinomas+with+frequent+methylationen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1209154en_HK
dc.identifier.pmid16247458-
dc.identifier.scopuseid_2-s2.0-33244483580en_HK
dc.identifier.hkuros114702en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33244483580&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1070en_HK
dc.identifier.epage1080en_HK
dc.identifier.isiWOS:000235361000011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridYing, J=12645439800en_HK
dc.identifier.scopusauthoridLi, H=24468545300en_HK
dc.identifier.scopusauthoridSeng, TJ=36957321000en_HK
dc.identifier.scopusauthoridLangford, C=7102621963en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridPutti, T=8341352700en_HK
dc.identifier.scopusauthoridMurray, P=7402596599en_HK
dc.identifier.scopusauthoridChan, ATC=13404833700en_HK
dc.identifier.scopusauthoridTao, Q=7102578359en_HK
dc.identifier.citeulike346774-

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