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Article: Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line

TitleConstitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line
Authors
Issue Date2004
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal Of Cancer, 2004, v. 91 n. 7, p. 1335-1341 How to Cite?
AbstractThe interleukin-mediated Janus kinase (JAK)/STAT pathway plays a crucial role in carcinogenesis. Recently, increased STAT3 activity was found in hepatocellular carcinoma and multiple myeloma in which there was silencing of SOCS-1 (suppressor of cytokine signalling-1) by gene promoter hypermethylation. We investigated the expression level of interleukin-6 (IL-6) and SOCS-1 in gastric cancer cell lines. Expression of SOCS-1 correlated with IL-6 level in most of the cell lines, except for AGS cells in which SOCS-1 was absent despite a high level of IL-6 production. Methylation analysis by methylation-specific polymerase chain reaction and bisulphite sequencing revealed that CpG island of SOCS-1 was densely methylated in AGS cells. Demethylation treatment by 5′azadeoxycytidine restored SOCS-1 expression and also suppressed constitutive STAT3 phosphorylation in AGS cells. Moreover, methylation of SOCS-1 was detected in 27.5% (11 of 40) of primary gastric tumours samples, 10% (one of 10) of adjacent noncancer tissues but not in any (zero of nine) normal gastric mucosa. Methylation of SOCS-1 also correlated with the loss of mRNA expression in some primary gastric cancers. In conclusion, this is the first report to demonstrate that hypermethylation of SOCS-1 led to gene silencing in gastric cancer cell line and primary tumour samples. Downregulation of SOCS-1 cooperates with IL-6 in the activation of JAK/STAT pathway in gastric cancer. © 2004 Cancer Research UK.
Persistent Identifierhttp://hdl.handle.net/10722/163269
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTo, KFen_US
dc.contributor.authorChan, MWYen_US
dc.contributor.authorLeung, WKen_US
dc.contributor.authorNg, EKWen_US
dc.contributor.authorYu, Jen_US
dc.contributor.authorBai, AHCen_US
dc.contributor.authorLo, AWIen_US
dc.contributor.authorChu, SHen_US
dc.contributor.authorTong, JHMen_US
dc.contributor.authorLo, KWen_US
dc.contributor.authorSung, JJYen_US
dc.contributor.authorChan, FKLen_US
dc.date.accessioned2012-09-05T05:29:23Z-
dc.date.available2012-09-05T05:29:23Z-
dc.date.issued2004en_US
dc.identifier.citationBritish Journal Of Cancer, 2004, v. 91 n. 7, p. 1335-1341en_US
dc.identifier.issn0007-0920en_US
dc.identifier.urihttp://hdl.handle.net/10722/163269-
dc.description.abstractThe interleukin-mediated Janus kinase (JAK)/STAT pathway plays a crucial role in carcinogenesis. Recently, increased STAT3 activity was found in hepatocellular carcinoma and multiple myeloma in which there was silencing of SOCS-1 (suppressor of cytokine signalling-1) by gene promoter hypermethylation. We investigated the expression level of interleukin-6 (IL-6) and SOCS-1 in gastric cancer cell lines. Expression of SOCS-1 correlated with IL-6 level in most of the cell lines, except for AGS cells in which SOCS-1 was absent despite a high level of IL-6 production. Methylation analysis by methylation-specific polymerase chain reaction and bisulphite sequencing revealed that CpG island of SOCS-1 was densely methylated in AGS cells. Demethylation treatment by 5′azadeoxycytidine restored SOCS-1 expression and also suppressed constitutive STAT3 phosphorylation in AGS cells. Moreover, methylation of SOCS-1 was detected in 27.5% (11 of 40) of primary gastric tumours samples, 10% (one of 10) of adjacent noncancer tissues but not in any (zero of nine) normal gastric mucosa. Methylation of SOCS-1 also correlated with the loss of mRNA expression in some primary gastric cancers. In conclusion, this is the first report to demonstrate that hypermethylation of SOCS-1 led to gene silencing in gastric cancer cell line and primary tumour samples. Downregulation of SOCS-1 cooperates with IL-6 in the activation of JAK/STAT pathway in gastric cancer. © 2004 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.meshCarrier Proteins - Biosynthesis - Metabolismen_US
dc.subject.meshCell Transformation, Neoplasticen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDna-Binding Proteins - Pharmacologyen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshHumansen_US
dc.subject.meshInterleukin-6 - Pharmacologyen_US
dc.subject.meshIntracellular Signaling Peptides And Proteinsen_US
dc.subject.meshJanus Kinase 1en_US
dc.subject.meshProtein-Tyrosine Kinases - Pharmacologyen_US
dc.subject.meshRna, Messenger - Analysis - Biosynthesisen_US
dc.subject.meshRepressor Proteins - Biosynthesis - Metabolismen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshStat3 Transcription Factoren_US
dc.subject.meshStomach Neoplasms - Pathologyen_US
dc.subject.meshSuppressor Of Cytokine Signaling Proteinsen_US
dc.subject.meshTrans-Activators - Pharmacologyen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.titleConstitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell lineen_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.6602133en_US
dc.identifier.pmid15354212en_US
dc.identifier.scopuseid_2-s2.0-6944250441en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-6944250441&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume91en_US
dc.identifier.issue7en_US
dc.identifier.spage1335en_US
dc.identifier.epage1341en_US
dc.identifier.isiWOS:000224250400017-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridTo, KF=24336843300en_US
dc.identifier.scopusauthoridChan, MWY=7402597788en_US
dc.identifier.scopusauthoridLeung, WK=7201504523en_US
dc.identifier.scopusauthoridNg, EKW=7201647539en_US
dc.identifier.scopusauthoridYu, J=35351306800en_US
dc.identifier.scopusauthoridBai, AHC=7006523130en_US
dc.identifier.scopusauthoridLo, AWI=7102780722en_US
dc.identifier.scopusauthoridChu, SH=8123479400en_US
dc.identifier.scopusauthoridTong, JHM=7202724564en_US
dc.identifier.scopusauthoridLo, KW=24302880900en_US
dc.identifier.scopusauthoridSung, JJY=35405352400en_US
dc.identifier.scopusauthoridChan, FKL=7202586434en_US

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