File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Linkage between STAT regulation and Epstein-Barr virus gene expression in tumors

TitleLinkage between STAT regulation and Epstein-Barr virus gene expression in tumors
Authors
Issue Date2001
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2001, v. 75 n. 6, p. 2929-2937 How to Cite?
AbstractEpstein-Barr virus (EBV) latency gene expression in lymphoblastoid cell lines is regulated by EBNA2. However, the factors regulating viral expression in EBV-associated tumors that do not express EBNA2 are poorly understood. In EBV-associated tumors, EBNA1 and frequently LMP1 are synthesized. We found that an alternative latent membrane protein 1 (LMP1) promoter, L1-TR, located within the terminal repeats is active in both nasopharyngeal carcinoma and Hodgkin's disease tissues. Examination of the L1-TR and the standard ED-L1 LMP1 promoters in electrophoretic mobility shift assays revealed that both promoters contain functional STAT binding sites. Further, both LMP1 promoters responded in reporter assays to activation of JAK-STAT signaling. Cotransfection of JAK1 or v-Src or treatment of cells with the cytokine interleukin-6 upregulated expression from ED-L1 and L1-TR reporter plasmids. Cotransfection of a dominant negative STAT3β revealed that STAT3 is likely to be the biologically relevant STAT for EBNA1 Qp and LMP1 L1-TR promoter regulation. In contrast, LMP1 expression from ED-L1 was not abrogated by STAT3β, indicating that the two LMP1 promoters are regulated by different STAT family members. Taken together with the previous demonstration of JAK-STAT activation of Qp driven EBNA1 expression, this places two of the EBV genes most commonly expressed in tumors under the control of the same signal transduction pathway. Immunohistochemical analyses of nasopharyngeal carcinoma tumors revealed that STAT3, STAT5, and STAT1 are constitutively activated in these tumors while STAT3 is constitutively activated in the malignant cells of Hodgkin's disease. We hypothesize that chronic or aberrant STAT activation may be both a necessary and predisposing event for EBV-driven tumorigenesis in immunocompetent individuals.
Persistent Identifierhttp://hdl.handle.net/10722/157328
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Hen_US
dc.contributor.authorLee, JMen_US
dc.contributor.authorZong, Yen_US
dc.contributor.authorBorowitz, Men_US
dc.contributor.authorNg, MHen_US
dc.contributor.authorAmbinder, RFen_US
dc.contributor.authorHayward, SDen_US
dc.date.accessioned2012-08-08T08:48:57Z-
dc.date.available2012-08-08T08:48:57Z-
dc.date.issued2001en_US
dc.identifier.citationJournal Of Virology, 2001, v. 75 n. 6, p. 2929-2937en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157328-
dc.description.abstractEpstein-Barr virus (EBV) latency gene expression in lymphoblastoid cell lines is regulated by EBNA2. However, the factors regulating viral expression in EBV-associated tumors that do not express EBNA2 are poorly understood. In EBV-associated tumors, EBNA1 and frequently LMP1 are synthesized. We found that an alternative latent membrane protein 1 (LMP1) promoter, L1-TR, located within the terminal repeats is active in both nasopharyngeal carcinoma and Hodgkin's disease tissues. Examination of the L1-TR and the standard ED-L1 LMP1 promoters in electrophoretic mobility shift assays revealed that both promoters contain functional STAT binding sites. Further, both LMP1 promoters responded in reporter assays to activation of JAK-STAT signaling. Cotransfection of JAK1 or v-Src or treatment of cells with the cytokine interleukin-6 upregulated expression from ED-L1 and L1-TR reporter plasmids. Cotransfection of a dominant negative STAT3β revealed that STAT3 is likely to be the biologically relevant STAT for EBNA1 Qp and LMP1 L1-TR promoter regulation. In contrast, LMP1 expression from ED-L1 was not abrogated by STAT3β, indicating that the two LMP1 promoters are regulated by different STAT family members. Taken together with the previous demonstration of JAK-STAT activation of Qp driven EBNA1 expression, this places two of the EBV genes most commonly expressed in tumors under the control of the same signal transduction pathway. Immunohistochemical analyses of nasopharyngeal carcinoma tumors revealed that STAT3, STAT5, and STAT1 are constitutively activated in these tumors while STAT3 is constitutively activated in the malignant cells of Hodgkin's disease. We hypothesize that chronic or aberrant STAT activation may be both a necessary and predisposing event for EBV-driven tumorigenesis in immunocompetent individuals.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshCell Lineen_US
dc.subject.meshDna-Binding Proteins - Genetics - Metabolismen_US
dc.subject.meshGene Expression Regulation, Viralen_US
dc.subject.meshHerpesvirus 4, Human - Genetics - Metabolism - Pathogenicityen_US
dc.subject.meshHodgkin Disease - Metabolism - Virologyen_US
dc.subject.meshHumansen_US
dc.subject.meshNasopharyngeal Neoplasms - Metabolism - Virologyen_US
dc.subject.meshPromoter Regions, Genetic - Geneticsen_US
dc.subject.meshProtein-Tyrosine Kinases - Metabolismen_US
dc.subject.meshStat3 Transcription Factoren_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTrans-Activators - Genetics - Metabolismen_US
dc.subject.meshViral Matrix Proteins - Genetics - Metabolismen_US
dc.subject.meshVirus Latencyen_US
dc.titleLinkage between STAT regulation and Epstein-Barr virus gene expression in tumorsen_US
dc.typeArticleen_US
dc.identifier.emailChen, H:hlchen@hkucc.hku.hken_US
dc.identifier.authorityChen, H=rp00383en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/JVI.75.6.2929-2937.2001en_US
dc.identifier.pmid11222718-
dc.identifier.scopuseid_2-s2.0-0035123574en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035123574&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume75en_US
dc.identifier.issue6en_US
dc.identifier.spage2929en_US
dc.identifier.epage2937en_US
dc.identifier.isiWOS:000167160400046-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChen, H=26643315400en_US
dc.identifier.scopusauthoridLee, JM=24177059700en_US
dc.identifier.scopusauthoridZong, Y=7005203474en_US
dc.identifier.scopusauthoridBorowitz, M=18041764400en_US
dc.identifier.scopusauthoridNg, MH=7202076421en_US
dc.identifier.scopusauthoridAmbinder, RF=7005598325en_US
dc.identifier.scopusauthoridHayward, SD=7102776214en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats