Comparative expression pathway analysis of human and canine mammary tumors

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.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.The availability of predictive preclinical animal models for human breast tumours represents a major challenge in breast cancer research. In vivo mouse models such as xenografts and transgenics, although widely used, have been demonstrated to fail in recapitulating essential features of human breast cancers such as heterogeneity, tumour microenvironment and dependence on steroid hormones [1,2]. Besides the intrinsic evolutionary distance between mice and humans, additional differences can originate from induced genetic modifications (transgenic mice) or from the altered presence of adjacent normal tissue, stromal cells, vasculature and immune system components (xenografts) [3-7]. Together these factors translate into a limited value of these mouse models for the study of cancer pathogenesis, progression and therapy, and represent a major obstacle to the identification of reliable predictive molecular biomarkers and the development of effective therape