Comparative expression pathway analysis of human and canine mammary tumors

doi:10.1186/1471-2164-10-135

BMC Genomics
Volume 10

Viewing options:

Abstract
Full text
PDF (2.5MB)
Additional files

Associated material:

Related literature:

Articles citing this article
on Google Scholar
on ISI Web of Science
on PubMed Central
Other articles by authors
on Google Scholar

Uva P
Aurisicchio L
Watters J
Loboda A
Kulkarni A
Castle J
Palombo F
Viti V
Mesiti G
Zappulli V
Marconato L
Abramo F
Ciliberto G
Lahm A
La Monica N
de Rinaldis E

on PubMed

Uva P
Aurisicchio L
Watters J
Loboda A
Kulkarni A
Castle J
Palombo F
Viti V
Mesiti G
Zappulli V
Marconato L
Abramo F
Ciliberto G
Lahm A
La Monica N
de Rinaldis E
Related articles/pages
on Google

on Google Scholar

on PubMed

Tools:

Nominate for award

Post to:

Research article

Comparative expression pathway analysis of human and canine mammary tumors

Paolo Uva¹ , Luigi Aurisicchio¹ , James Watters² , Andrey Loboda² , Amit Kulkarni³ , John Castle³ , Fabio Palombo¹ , Valentina Viti¹ , Giuseppe Mesiti¹ , Valentina Zappulli⁴ , Laura Marconato⁵ , Francesca Abramo⁶ , Gennaro Ciliberto¹ , Armin Lahm¹ , Nicola La Monica¹ and Emanuele de Rinaldis¹

¹IRBM P. Angeletti, Merck MRL-Rome, Via Pontina Km, 30600 Pomezia, Italy

²Department of Molecular Profiling, Merck Research Laboratories, West Point, Pennsylvania, USA

³Rosetta Inpharmatics LLC, a wholly owned subsidiary of Merck and Co Inc., Terry Avenue North, Seattle, WA 98109, USA

⁴Department of Public Health, Veterinary Hygiene and Comparative Pathology, University of Padua, Italy

⁵Clinica Veterinaria L'Arca, Vico Cacciottoli 46/47, 80129 Naples, Italy

⁶Department of Animal Pathology, University of Pisa, Italy

author email corresponding author email

BMC Genomics 2009, 10:135doi:10.1186/1471-2164-10-135


Published:	27 March 2009

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.

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.