Publicação
Differential expression of GSPT1 GGCn alleles in cancer
| Resumo: | The 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. |
|---|---|
| Autores principais: | Malta-Vacas, Joana |
| Outros Autores: | Ferreira, Paula; Monteiro, Carolino; Brito, Miguel |
| Assunto: | Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| Ano: | 2009 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Científico do Instituto Politécnico de Lisboa |
| _version_ | 1866887352307154944 |
|---|---|
| author | Malta-Vacas, Joana |
| author2 | Ferreira, Paula Monteiro, Carolino Brito, Miguel |
| author2_role | author author author |
| author_facet | Malta-Vacas, Joana Ferreira, Paula Monteiro, Carolino Brito, Miguel |
| author_role | author |
| contributor_name_str_mv | RCIPL |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Malta-Vacas, Joana\"},{\"Person.name\":\"Ferreira, Paula\"},{\"Person.name\":\"Monteiro, Carolino\"},{\"Person.name\":\"Brito, Miguel\",\"Person.identifier.orcid\":\"0000-0001-6394-658X\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RCIPL |
| datacite.creators.creator.creatorName.fl_str_mv | Malta-Vacas, Joana Ferreira, Paula Monteiro, Carolino Brito, Miguel |
| datacite.date.Accepted.fl_str_mv | 2009-12-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2014-01-04T17:53:44Z |
| datacite.date.embargoed.fl_str_mv | 2014-01-04T17:53:44Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| datacite.titles.title.fl_str_mv | Differential expression of GSPT1 GGCn alleles in cancer |
| dc.contributor.none.fl_str_mv | RCIPL |
| dc.creator.none.fl_str_mv | Malta-Vacas, Joana Ferreira, Paula Monteiro, Carolino Brito, Miguel |
| dc.date.Accepted.fl_str_mv | 2009-12-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2014-01-04T17:53:44Z |
| dc.date.embargoed.fl_str_mv | 2014-01-04T17:53:44Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.21/3071 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| dc.title.fl_str_mv | Differential expression of GSPT1 GGCn alleles in cancer |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | The 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ipl.pt/bitstreams/bb237ff9-f73a-40ba-aa7f-789abc039c9c/download |
| id | ripl_2e41b54c6bd2405eba8a92585437110f |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.21/3071 |
| instacron_str | ipl |
| institution | Instituto Politécnico de Lisboa |
| instname_str | Instituto Politécnico de Lisboa |
| language | eng |
| network_acronym_str | ripl |
| network_name_str | Repositório Científico do Instituto Politécnico de Lisboa |
| oai_identifier_str | oai:repositorio.ipl.pt:10400.21/3071 |
| organization_str_mv | urn:organizationAcronym:ipl |
| person_str_mv | Malta-Vacas, Joana Ferreira, Paula Monteiro, Carolino Brito, Miguel Brito, Miguel https://www.ciencia-id.pt/231F-F341-7E93 231F-F341-7E93 http://orcid.org/0000-0001-6394-658X 0000-0001-6394-658X |
| publishDate | 2009 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | Repositório Científico do Instituto Politécnico de Lisboa |
| repository_id_str | urn:repositoryAcronym:ripl |
| service_str_mv | urn:repositoryAcronym:ripl |
| spelling | engElsevierporThe 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.application/pdfporDifferential expression of GSPT1 GGCn alleles in cancerMalta-Vacas, JoanaFerreira, PaulaMonteiro, CarolinoPersonalBrito, MiguelDSpacehttp://dspace.org/items/4252d8e0-800c-4d67-8b13-0b711d860669DSpacehttp://dspace.org/items/4252d8e0-800c-4d67-8b13-0b711d860669BritoMiguelCiência IDhttps://www.ciencia-id.pt231F-F341-7E93ORCIDhttp://orcid.org0000-0001-6394-658XResearcher IDhttps://www.researcherid.comA-7970-2016Scopus Author IDhttps://www.scopus.com35224551000Scopus Author IDhttps://www.scopus.com57200288349HostingInstitutionOrganizationalRCIPLe-mailmailto:rcaap@sp.ipl.ptrcaap@sp.ipl.ptISSNIsPartOf1873-44562014-01-04T17:53:44Z2009-122009-12-01T00:00:00ZHandlehttp://hdl.handle.net/10400.21/3071http://purl.org/coar/access_right/c_abf2open accessAllelesBase sequenceColorectal neoplasmsDNA methylationDNA primersFlow cytometryGene expressionMicronucleus testsPeptide termination factorsRNA, MessengerReverse transcriptase polymerase chain reactionTandem repeat sequences290078 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ipl.pt/bitstreams/bb237ff9-f73a-40ba-aa7f-789abc039c9c/downloadCancer Genetics and Cytogenetics195132142 |
| spellingShingle | Differential expression of GSPT1 GGCn alleles in cancer Malta-Vacas, Joana Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| status | SINGLETON |
| subject.fl_str_mv | Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| title | Differential expression of GSPT1 GGCn alleles in cancer |
| title_full | Differential expression of GSPT1 GGCn alleles in cancer |
| title_fullStr | Differential expression of GSPT1 GGCn alleles in cancer |
| title_full_unstemmed | Differential expression of GSPT1 GGCn alleles in cancer |
| title_short | Differential expression of GSPT1 GGCn alleles in cancer |
| title_sort | Differential expression of GSPT1 GGCn alleles in cancer |
| topic | Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| topic_facet | Alleles Base sequence Colorectal neoplasms DNA methylation DNA primers Flow cytometry Gene expression Micronucleus tests Peptide termination factors RNA, Messenger Reverse transcriptase polymerase chain reaction Tandem repeat sequences |
| url | http://hdl.handle.net/10400.21/3071 |
| visible | 1 |