title: 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.
abstract: Human 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.
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Santos
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal ; Veterinary Clinics of University of Porto, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Cláudia S
authors.initials: CS
authors.lastname: Baptista
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal ; CIMO-ESA, Instituto Politécnico de Bragança, Bragança, Portugal.
authors.forename: Rui M V
authors.initials: RM
authors.lastname: Abreu
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal ; Department of Genetics and Biotechnology, School of Life Sciences and Environment, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Estela
authors.initials: E
authors.lastname: Bastos
authors.affiliation: Institute of Pathology and Immunology, University of Porto, Porto, Portugal ; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Irina
authors.initials: I
authors.lastname: Amorim
authors.affiliation: Centre National de Genotypage, Evry, France.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.affiliation: Institute of Pathology and Immunology, University of Porto, Porto, Portugal ; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal ; Department of Genetics and Biotechnology, School of Life Sciences and Environment, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Chaves
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002415:Cats; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018734:Genes, erbB-2; D014644:Genetic Variation; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012313:RNA / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D012313:RNA