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Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein

2012-04-27Journal article Open access
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dc.contributor.authorAlmeida, Sílvia Cristina Paiva
dc.contributor.authorde Oliveira, Vivian Leite
dc.contributor.authorVentura, Sónia
dc.contributor.authorBofill, Margarita
dc.contributor.authorParkhouse, Robert Michael Evans
dc.date.accessioned2016-06-21T15:09:30Z
dc.date.available2016-06-21T15:09:30Z
dc.date.issued2012-04-27
dc.description.abstractVirus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-κB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4(+)CD8(+)CD69(-) lymphoma. The CD4(+)CD8(+)CD69(-) cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-κB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCRβ-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4(+)CD8(+)CD69(-) thymocytes from A238L transgenic mice was consistent with the phenotype. Similarly evaluated expression profiles of CD4(+)CD8(+) CD69(-) thymocytes from the mutant A238L transgenic mice were comparable to those of wild type mice. These features, together with the demonstration of (mono-)oligoclonality, suggest a transgene-NFAT-dependent transformation yielding a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas.pt_PT
dc.description.sponsorshipFundação para a Ciência e Tecnologia grants: (SFRH/BD/882/2000, POCTI/2000/MGI/36403); Ministério da Ciência e Ensino Superior.pt_PT
dc.identifier.citationAlmeida SCP, de Oliveira VL, Ventura S, Bofill M, Parkhouse RME (2012) Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein. PLoS ONE 7(4): e34140. doi:10.1371/journal.pone.0034140pt_PT
dc.identifier.doi10.1371/journal.pone.0034140pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/659
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034140pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAnimalspt_PT
dc.subjectAntigens, CD4pt_PT
dc.subjectAntigens, CD8pt_PT
dc.subjectBase Sequencept_PT
dc.subjectBlotting, Southernpt_PT
dc.subjectCell Transformation, Neoplasticpt_PT
dc.subjectDNA Primerspt_PT
dc.subjectFlow Cytometrypt_PT
dc.subjectFluorescent Antibody Techniquept_PT
dc.subjectGene Dosagept_PT
dc.subjectGene Expression Profilingpt_PT
dc.subjectHistological Techniquespt_PT
dc.subjectLymphomapt_PT
dc.subjectMicept_PT
dc.subjectMice, Transgenicpt_PT
dc.subjectMolecular Sequence Datapt_PT
dc.subjectNFATC Transcription Factorspt_PT
dc.subjectNeovascularization, Pathologicpt_PT
dc.subjectPlasmidspt_PT
dc.subjectSequence Analysis, DNApt_PT
dc.subjectT-Lymphocytespt_PT
dc.subjectThymocytespt_PT
dc.subjectViral Proteinspt_PT
dc.subjectGene Transfer Techniquespt_PT
dc.titleNeoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Proteinpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/WT/075813
oaire.citation.endPage13pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLoS ONEpt_PT
oaire.citation.volume7pt_PT
oaire.fundingStream075813
project.funder.identifierhttp://doi.org/10.13039/100010269
project.funder.nameWellcome Trust
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication05711d13-46a9-43b1-a262-3e4e92ff772f
relation.isProjectOfPublication.latestForDiscovery05711d13-46a9-43b1-a262-3e4e92ff772f

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