Molecular characterization of cancer critical genes in feline mammary carcinomas and in the FkMTp cell line
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2018-01-10
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Os tumores da mama são uma doença complexa que põe em perigo a vida de muitas pessoas em todo o mundo. Tal como outros tipos de cancro, o cancro da mama necessita de um modelo adequado que permita, não só, que se perceba melhor a origem e os mecanismos envolvidos na tumorigénese, mas também um modelo que permita a realização de testagem de novas terapias. Neste sentido, o Felis catus tem surgido ao longo dos anos como um modelo importante para o estudo do cancro da mama humano uma vez que esta espécie é afetada, espontaneamente, com grande frequência por tumores mamários, que são em muitos aspetos, nomeadamente histológica e clinicopatologicamente muito semelhantes aos tumores da mama da mulher. Além disso, o estilo de vida mais humanizado do gato, fruto da grande convivência entre as duas espécies implica que partilhem dos mesmos fatores de risco ambientais. Com este trabalho pretendemos estudar molecularmente os carcinomas mamários felinos e descobrir potenciais candidatos a biomarcadores. Para tal, avaliámos, através de quantificação absoluta por PCR em tempo real, algumas sequências: HER2, TP53, TOP2α, Cyclin D1, FUS, YBX1, PTBP1, c-Myc, PKM2 e FA-SAT, algumas delas tanto a nível do DNA como do RNA e outras apenas ao nível do RNA, numa coleção de carcinomas mamários felinos e numa linha celular tumoral de gata, a linha FkMTp. Na análise dos tumores os resultados da expressão foram correlacionados com parâmetros clinicopatológicos como por exemplo o tamanho do tumor, a classificação molecular ou tumores múltiplos, entre outros. Os nossos resultados nos tumores mamários felinos mostram padrões de expressão muito semelhantes àqueles que são reportados na mulher acentuando as similaridades nas vias moleculares envolvidas em ambas as doenças, aumentando assim as evidências que apontam o gato doméstico como um bom modelo para o estudo do cancro da mama em humano. Relativamente à linha celular concluímos que pode ser uma linha celular de interesse no estudo de tumores classificados como HER2 positivos sem amplificação génica.
Breast tumours are a complex disease endangering the lives of many people around the world. As other cancers, breast cancer needs suitable models in order to uncover the mechanisms underlying tumorigenesis and that allow the performance of clinical tests of new therapies. In this sense, Felis catus has been over the years emerging as a valuable model to study breast cancer once it is greatly affected by spontaneous mammary tumours which are, in many aspects such as clinicopathologically and histologically, similar to human breast tumours. Moreover, the humanized lifestyle of the domestic cat makes it share the same environmental risk factors as humans. With this work we intended to study molecularly Feline mammary carcinomas and potentially uncover some potential biomarker candidate. To do so, we evaluated, through absolute quantification by Real Time qPCR, a few sequences: HER2, TP53, TOP2α, Cyclin D1, FUS, YBX1, PTBP1, c-Myc, PKM2 and FA-SAT, some of them at both DNA and RNA levels and others only at the RNA level in a collection of feline mammary carcinomas and in the FkMTp feline cell line. In the tumour analysis, we correlated the expression data with clinicopathological parameters, such as tumour size, molecular classification, multiple tumours, among others. Our results in the feline mammary tumours show expression patterns very similar to what is already reported in women, highlighting the similarity in the molecular pathways involved in both diseases, increasing the evidences supporting Felis catus as a good human breast cancer model. Regarding the feline cell line it was observed that it could be a cell line of interest in the study of HER2 positive tumours that are negative for gene amplification.
Breast tumours are a complex disease endangering the lives of many people around the world. As other cancers, breast cancer needs suitable models in order to uncover the mechanisms underlying tumorigenesis and that allow the performance of clinical tests of new therapies. In this sense, Felis catus has been over the years emerging as a valuable model to study breast cancer once it is greatly affected by spontaneous mammary tumours which are, in many aspects such as clinicopathologically and histologically, similar to human breast tumours. Moreover, the humanized lifestyle of the domestic cat makes it share the same environmental risk factors as humans. With this work we intended to study molecularly Feline mammary carcinomas and potentially uncover some potential biomarker candidate. To do so, we evaluated, through absolute quantification by Real Time qPCR, a few sequences: HER2, TP53, TOP2α, Cyclin D1, FUS, YBX1, PTBP1, c-Myc, PKM2 and FA-SAT, some of them at both DNA and RNA levels and others only at the RNA level in a collection of feline mammary carcinomas and in the FkMTp feline cell line. In the tumour analysis, we correlated the expression data with clinicopathological parameters, such as tumour size, molecular classification, multiple tumours, among others. Our results in the feline mammary tumours show expression patterns very similar to what is already reported in women, highlighting the similarity in the molecular pathways involved in both diseases, increasing the evidences supporting Felis catus as a good human breast cancer model. Regarding the feline cell line it was observed that it could be a cell line of interest in the study of HER2 positive tumours that are negative for gene amplification.
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Cancro da mama , Carcinomas mamários felinos , PCR em tempo real , HER2