File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Epigenetic disruption of interferon-γ response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomas

TitleEpigenetic disruption of interferon-γ response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomas
Authors
KeywordsCarcinoma
CpG island
IRF8
Methylation
Tumor suppressor gene
Issue Date2008
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2008, v. 27 n. 39, p. 5267-5276 How to Cite?
Abstract
16q24 is frequently deleted in multiple tumors including cancers of nasopharynx, esophagus, breast, prostate and liver. By array comparative genomic hybridization (aCGH), we refined a 16q24 hemizygous deletion in nasopharyngeal carcinoma (NPC) cell lines. Semi-quantitative RT-PCR analysis revealed interferon regulatory factor 8 (IRF8) as the only downregulated gene within this deletion. IRF8 belongs to a family of interferon (IFN) regulatory factors that modulate various important physiologic processes including host defense, cell growth and differentiation and immune regulation. In contrast to the broad expression of IRF8 in normal adult and fetal tissues, transcriptional silencing and promoter methylation of IRF8 were frequently detected in multiple carcinoma (except for hepatocellular) cell lines (100% in NPC, 88% in esophageal and 18-78% in other carcinoma cell lines) and in a large collection of primary carcinomas (78% in NPC, 36-71% in other carcinomas). Methylation of the IRF8 promoter led to the disruption of its response to IFN-γ stimulation. Pharmacological and genetic demethylation could restore IRF8 expression, indicating a direct epigenetic mechanism. Ectopic expression of IRF8 in tumor cells lacking its expression strongly inhibited their clonogenicity, confirming its tumor suppressor function. Thus, IRF8 was identified as a functional tumor suppressor, which is frequently silenced by epigenetic mechanism in multiple carcinomas. © 2008 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/148578
ISSN
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
ISI Accession Number ID
Funding AgencyGrant Number
Michael and Betty Kadoorie Cancer Genetics Research Program (MBKCGRP)
Hong Kong RGC Central Allocation GrantCA06/07.SC03
Funding Information:

This project was supported by a Michael and Betty Kadoorie Cancer Genetics Research Program (MBKCGRP) Grant to QT and a Hong Kong RGC Central Allocation Grant (CA06/07.SC03, QT). We thank Drs Bert Vogelstein, George Tsao (Dolly Huang), Sun Young Rha and Kaitai Yao for some cell lines, DSMZ (German Collection of Microorganisms and Cell Cultures) for the KYSE cell lines [Shimada et al., Cancer 69: 277-284 (1992)], Dr C Langford at the Wellcome Trust Sanger Institute, Cambridge, UK for aCGH slides, and Tzer- Jing Seng (Johns Hopkins Singapore) for her valuable help in aCGH analysis.

References

 

DC FieldValueLanguage
dc.contributor.authorLee, KYen_HK
dc.contributor.authorGeng, Hen_HK
dc.contributor.authorNg, KMen_HK
dc.contributor.authorYu, Jen_HK
dc.contributor.authorVan Hasselt, Aen_HK
dc.contributor.authorCao, Yen_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorWong, AHYen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorYing, Jen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorLung, MLen_HK
dc.contributor.authorWang, LDen_HK
dc.contributor.authorKwok, TTen_HK
dc.contributor.authorLevi, BZen_HK
dc.contributor.authorChan, ATCen_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2012-05-29T06:13:51Z-
dc.date.available2012-05-29T06:13:51Z-
dc.date.issued2008en_HK
dc.identifier.citationOncogene, 2008, v. 27 n. 39, p. 5267-5276en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148578-
dc.description.abstract16q24 is frequently deleted in multiple tumors including cancers of nasopharynx, esophagus, breast, prostate and liver. By array comparative genomic hybridization (aCGH), we refined a 16q24 hemizygous deletion in nasopharyngeal carcinoma (NPC) cell lines. Semi-quantitative RT-PCR analysis revealed interferon regulatory factor 8 (IRF8) as the only downregulated gene within this deletion. IRF8 belongs to a family of interferon (IFN) regulatory factors that modulate various important physiologic processes including host defense, cell growth and differentiation and immune regulation. In contrast to the broad expression of IRF8 in normal adult and fetal tissues, transcriptional silencing and promoter methylation of IRF8 were frequently detected in multiple carcinoma (except for hepatocellular) cell lines (100% in NPC, 88% in esophageal and 18-78% in other carcinoma cell lines) and in a large collection of primary carcinomas (78% in NPC, 36-71% in other carcinomas). Methylation of the IRF8 promoter led to the disruption of its response to IFN-γ stimulation. Pharmacological and genetic demethylation could restore IRF8 expression, indicating a direct epigenetic mechanism. Ectopic expression of IRF8 in tumor cells lacking its expression strongly inhibited their clonogenicity, confirming its tumor suppressor function. Thus, IRF8 was identified as a functional tumor suppressor, which is frequently silenced by epigenetic mechanism in multiple carcinomas. © 2008 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
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.subjectCpG islanden_HK
dc.subjectIRF8en_HK
dc.subjectMethylationen_HK
dc.subjectTumor suppressor geneen_HK
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshEpigenesis, Geneticen_US
dc.subject.meshEsophageal Neoplasms - Geneticsen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshHumansen_US
dc.subject.meshInterferon Regulatory Factors - Geneticsen_US
dc.subject.meshInterferon-Gamma - Physiologyen_US
dc.subject.meshNasopharyngeal Neoplasms - Geneticsen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.titleEpigenetic disruption of interferon-γ response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomasen_HK
dc.typeArticleen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.emailLung, ML:mlilung@hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2008.147en_HK
dc.identifier.pmid18469857en_HK
dc.identifier.scopuseid_2-s2.0-51349083104en_HK
dc.identifier.hkuros150716-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-51349083104&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume27en_HK
dc.identifier.issue39en_HK
dc.identifier.spage5267en_HK
dc.identifier.epage5276en_HK
dc.identifier.isiWOS:000258915100011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLee, KY=35080729700en_HK
dc.identifier.scopusauthoridGeng, H=36784950400en_HK
dc.identifier.scopusauthoridNg, KM=7403178872en_HK
dc.identifier.scopusauthoridYu, J=35351306800en_HK
dc.identifier.scopusauthoridVan Hasselt, A=6603932076en_HK
dc.identifier.scopusauthoridCao, Y=7404524499en_HK
dc.identifier.scopusauthoridZeng, YX=7402981579en_HK
dc.identifier.scopusauthoridWong, AHY=16743208300en_HK
dc.identifier.scopusauthoridWang, X=7501866464en_HK
dc.identifier.scopusauthoridYing, J=12645439800en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK
dc.identifier.scopusauthoridWang, LD=36066730500en_HK
dc.identifier.scopusauthoridKwok, TT=35196382300en_HK
dc.identifier.scopusauthoridLevi, BZ=7005252408en_HK
dc.identifier.scopusauthoridChan, ATC=13404833700en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridTao, Q=7102578359en_HK
dc.identifier.citeulike2791205-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats