title: Comparative expression pathway analysis of human and canine mammary tumors.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: IRBM P Angeletti, Merck MRL-Rome, Pomezia, Italy. paolo.uva@gmail.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Uva
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.forename: James
authors.initials: J
authors.lastname: Watters
authors.forename: Andrey
authors.initials: A
authors.lastname: Loboda
authors.forename: Amit
authors.initials: A
authors.lastname: Kulkarni
authors.forename: John
authors.initials: J
authors.lastname: Castle
authors.forename: Fabio
authors.initials: F
authors.lastname: Palombo
authors.forename: Valentina
authors.initials: V
authors.lastname: Viti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mesiti
authors.forename: Valentina
authors.initials: V
authors.lastname: Zappulli
authors.forename: Laura
authors.initials: L
authors.lastname: Marconato
authors.forename: Francesca
authors.initials: F
authors.lastname: Abramo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Armin
authors.initials: A
authors.lastname: Lahm
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Emanuele
authors.initials: E
authors.lastname: de Rinaldis