Research article
Comparative expression pathway analysis of human and canine mammary tumors
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* Corresponding author: Emanuele de Rinaldis emanuele_derinaldis@merck.com
1 IRBM P. Angeletti, Merck MRL-Rome, Via Pontina Km, 30600 Pomezia, Italy
2 Department of Molecular Profiling, Merck Research Laboratories, West Point, Pennsylvania, USA
3 Rosetta Inpharmatics LLC, a wholly owned subsidiary of Merck and Co Inc., Terry Avenue North, Seattle, WA 98109, USA
4 Department of Public Health, Veterinary Hygiene and Comparative Pathology, University of Padua, Italy
5 Clinica Veterinaria L'Arca, Vico Cacciottoli 46/47, 80129 Naples, Italy
6 Department of Animal Pathology, University of Pisa, Italy
BMC Genomics 2009, 10:135 doi:10.1186/1471-2164-10-135
Published: 27 March 2009Abstract
Background
Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved.
Results
We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries.
Conclusion
Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.