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Differential expression of GSPT1 GGCn alleles in cancer

dc.contributor.authorMalta-Vacas, Joana
dc.contributor.authorFerreira, Paula
dc.contributor.authorMonteiro, Carolino
dc.contributor.authorBrito, Miguel
dc.date.accessioned2014-01-04T17:53:44Z
dc.date.available2014-01-04T17:53:44Z
dc.date.issued2009-12
dc.description.abstractThe human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.por
dc.identifier.citationMalta-Vacas J, Ferreira P, Monteiro C, Brito M. Differential expression of GSPT1 GGCn alleles in cancer. Cancer Genet Cytogenet. 2009;195(2):132-42.por
dc.identifier.issn1873-4456
dc.identifier.urihttp://hdl.handle.net/10400.21/3071
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0165460809004300por
dc.subjectAllelespor
dc.subjectBase sequencepor
dc.subjectColorectal neoplasmspor
dc.subjectDNA methylationpor
dc.subjectDNA primerspor
dc.subjectFlow cytometrypor
dc.subjectGene expressionpor
dc.subjectMicronucleus testspor
dc.subjectPeptide termination factorspor
dc.subjectRNA, Messengerpor
dc.subjectReverse transcriptase polymerase chain reactionpor
dc.subjectTandem repeat sequencespor
dc.titleDifferential expression of GSPT1 GGCn alleles in cancerpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage142por
oaire.citation.startPage132por
oaire.citation.titleCancer Genetics and Cytogeneticspor
oaire.citation.volume195por
person.familyNameBrito
person.givenNameMiguel
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscovery4252d8e0-800c-4d67-8b13-0b711d860669

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