Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

<p>Abstract</p> <p>Background</p> <p>Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and t...

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Main Authors: Hummel Michael, Lenze Dido, Klopfleisch Robert, Gruber Achim D
Format: Article
Language:English
Published: BMC 2010-11-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/10/618
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author Hummel Michael
Lenze Dido
Klopfleisch Robert
Gruber Achim D
author_facet Hummel Michael
Lenze Dido
Klopfleisch Robert
Gruber Achim D
author_sort Hummel Michael
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent.</p> <p>Methods</p> <p>Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer.</p> <p>Results</p> <p>Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors.</p> <p>Conclusions</p> <p>Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.</p>
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spelling doaj.art-55b75e41a3714a288ae39bfde25bfdb42022-12-21T20:56:22ZengBMCBMC Cancer1471-24072010-11-0110161810.1186/1471-2407-10-618Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profilesHummel MichaelLenze DidoKlopfleisch RobertGruber Achim D<p>Abstract</p> <p>Background</p> <p>Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent.</p> <p>Methods</p> <p>Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer.</p> <p>Results</p> <p>Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors.</p> <p>Conclusions</p> <p>Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.</p>http://www.biomedcentral.com/1471-2407/10/618
spellingShingle Hummel Michael
Lenze Dido
Klopfleisch Robert
Gruber Achim D
Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
BMC Cancer
title Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
title_full Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
title_fullStr Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
title_full_unstemmed Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
title_short Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
title_sort metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
url http://www.biomedcentral.com/1471-2407/10/618
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AT klopfleischrobert metastaticcaninemammarycarcinomascanbeidentifiedbyageneexpressionprofilethatpartlyoverlapswithhumanbreastcancerprofiles
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