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Article: Absence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer

TitleAbsence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer
Authors
Issue Date2003
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal Of Cancer, 2003, v. 88 n. 10, p. 1560-1565 How to Cite?
AbstractExpression of cyclin D2 is absent in 30-70% of gastric cancers. We investigated the role of promoter hypermethylation in the transcriptional silencing of cyclin D2 in five gastric cell lines and 47 primary gastric carcinomas. CpG island methylation status of the cyclin D2 gene was studied by methylation-specific polymerase chain reaction and bisulphite sequencing. RNA and protein expression was analysed by reverse transcription-PCR and Western blot, respectively. Dense methylation of cyclin D2 was detected in three cell lines (KATOIII, AGS and NCI-N87), which also lacked cyclin D2 mRNA and protein expression. Bisulphite DNA sequencing revealed that loss ofcyclin D2 expression was closely associated with the density of methylation in the promoter region. Treatment with DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, restored the cyclin D2 expression level in methylated gastric cells. Among the 47 primary gastric cancers, cyclin D2 hypermethylation was detected in 23 (48.9%) cases. None of the 23 normal gastric biopsies from noncancer patients showed hypermethylation. Hypermethylation was associated with loss of mRNA (P < 0.001) and protein (p = 0.006) expressions. Our study showed that cyclin D2 hypermethylation is associated with loss of cyclin D2 expression in a subset of gastric cancers, which may suggest an alternative gastric carcinogenesis pathway in the absence of cyclin D2 expression. © 2003 Cancer Research UK.
Persistent Identifierhttp://hdl.handle.net/10722/162699
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYu, Jen_US
dc.contributor.authorLeung, WKen_US
dc.contributor.authorEbert, MPAen_US
dc.contributor.authorLeong, RWLen_US
dc.contributor.authorTse, PCHen_US
dc.contributor.authorChan, MWYen_US
dc.contributor.authorBai, AHCen_US
dc.contributor.authorTo, KFen_US
dc.contributor.authorMalfertheiner, Pen_US
dc.contributor.authorSung, JJYen_US
dc.date.accessioned2012-09-05T05:22:28Z-
dc.date.available2012-09-05T05:22:28Z-
dc.date.issued2003en_US
dc.identifier.citationBritish Journal Of Cancer, 2003, v. 88 n. 10, p. 1560-1565en_US
dc.identifier.issn0007-0920en_US
dc.identifier.urihttp://hdl.handle.net/10722/162699-
dc.description.abstractExpression of cyclin D2 is absent in 30-70% of gastric cancers. We investigated the role of promoter hypermethylation in the transcriptional silencing of cyclin D2 in five gastric cell lines and 47 primary gastric carcinomas. CpG island methylation status of the cyclin D2 gene was studied by methylation-specific polymerase chain reaction and bisulphite sequencing. RNA and protein expression was analysed by reverse transcription-PCR and Western blot, respectively. Dense methylation of cyclin D2 was detected in three cell lines (KATOIII, AGS and NCI-N87), which also lacked cyclin D2 mRNA and protein expression. Bisulphite DNA sequencing revealed that loss ofcyclin D2 expression was closely associated with the density of methylation in the promoter region. Treatment with DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, restored the cyclin D2 expression level in methylated gastric cells. Among the 47 primary gastric cancers, cyclin D2 hypermethylation was detected in 23 (48.9%) cases. None of the 23 normal gastric biopsies from noncancer patients showed hypermethylation. Hypermethylation was associated with loss of mRNA (P < 0.001) and protein (p = 0.006) expressions. Our study showed that cyclin D2 hypermethylation is associated with loss of cyclin D2 expression in a subset of gastric cancers, which may suggest an alternative gastric carcinogenesis pathway in the absence of cyclin D2 expression. © 2003 Cancer Research UK.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjcen_US
dc.relation.ispartofBritish Journal of Canceren_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarcinoma - Genetics - Pathologyen_US
dc.subject.meshCell Transformation, Neoplasticen_US
dc.subject.meshCyclin D2en_US
dc.subject.meshCyclins - Biosynthesisen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshHumansen_US
dc.subject.meshNerve Tissue Proteins - Biosynthesisen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshPromoter Regions, Genetic - Geneticsen_US
dc.subject.meshRna, Messenger - Analysisen_US
dc.subject.meshStomach Neoplasms - Genetics - Pathologyen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.titleAbsence of cyclin D2 expression is associated with promoter hypermethylation in gastric canceren_US
dc.typeArticleen_US
dc.identifier.emailLeung, WK:waikleung@hku.hken_US
dc.identifier.authorityLeung, WK=rp01479en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.bjc.6600940en_US
dc.identifier.pmid12771922-
dc.identifier.scopuseid_2-s2.0-0038455147en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0038455147&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume88en_US
dc.identifier.issue10en_US
dc.identifier.spage1560en_US
dc.identifier.epage1565en_US
dc.identifier.isiWOS:000183298700011-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYu, J=35351306800en_US
dc.identifier.scopusauthoridLeung, WK=7201504523en_US
dc.identifier.scopusauthoridEbert, MPA=35239660600en_US
dc.identifier.scopusauthoridLeong, RWL=24343912800en_US
dc.identifier.scopusauthoridTse, PCH=7005336892en_US
dc.identifier.scopusauthoridChan, MWY=7402597788en_US
dc.identifier.scopusauthoridBai, AHC=7006523130en_US
dc.identifier.scopusauthoridTo, KF=7101911940en_US
dc.identifier.scopusauthoridMalfertheiner, P=36048150200en_US
dc.identifier.scopusauthoridSung, JJY=35405352400en_US

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