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ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

dc.contributor.authorSantos, Sara
dc.contributor.authorBatista, Claudia S.
dc.contributor.authorAbreu, Rui M.V.
dc.contributor.authorBastos, Estela
dc.contributor.authorAmorim, Irina
dc.contributor.authorGut, Ivo G.
dc.contributor.authorGartner, Fátima
dc.contributor.authorChaves, Raquel
dc.date.accessioned2014-07-08T09:39:26Z
dc.date.available2014-07-08T09:39:26Z
dc.date.issued2013
dc.description.abstractHuman ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC.por
dc.description.sponsorshipPOCI/CVT/62940/2004 and by the PhD grants (SFRH/BD/23406/2005 and SFRH/BD/31754/2006, of the Science and Technology Foundation (FCT) from Portugal.por
dc.identifier.citationSantos, Sara; Batista, Claudia; Abreu, Rui M.V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gartner, Fátima; Chaves, Raquel (2013). ERBB2 in cat mammary neoplasias disclosed a positive correlation between rna and protein low expression levels: a model for erbb-2 negative human breast câncer. Plos One. ISSN 1932-6203. 8:12, p. e83673-e83673por
dc.identifier.doi10.1371/journal.pone.0083673
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10198/9855
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherPLOSpor
dc.relationGENÓMICA FUNCIONAL E ESTABELECIMENTO DE LINHAS CELULARES EM TUMORES MAMÁRIOS DE GATA CMT
dc.relationTHE METASTATIC PROCESS IN CAT MAMMARY TUMOURS – GENOMIC AND FUNCTIONAL CHARACTERIZATION OF CANDIDATE GENES
dc.titleERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancerpor
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGENÓMICA FUNCIONAL E ESTABELECIMENTO DE LINHAS CELULARES EM TUMORES MAMÁRIOS DE GATA CMT
oaire.awardTitleTHE METASTATIC PROCESS IN CAT MAMMARY TUMOURS – GENOMIC AND FUNCTIONAL CHARACTERIZATION OF CANDIDATE GENES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCI%2FCVT%2F62940%2F2004/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F23406%2F2005/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F31754%2F2006/PT
oaire.citation.endPagee83673por
oaire.citation.startPagee83673por
oaire.citation.titlePlos Onepor
oaire.citation.volume8 (12)por
oaire.fundingStreamPOCI
oaire.fundingStreamFARH
oaire.fundingStreamFARH
person.familyNameAbreu
person.givenNameRui M.V.
person.identifier.ciencia-id0F19-0DE2-12A2
person.identifier.orcid0000-0002-7745-8015
person.identifier.scopus-author-id7003290613
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspor
rcaap.typearticlepor
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