Carcinogenesis Advance Access originally published online on April 21, 2005
Carcinogenesis 2005 26(8):1343-1353; doi:10.1093/carcin/bgi100
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Carcinogenesis vol.26 no.8 © Oxford University Press 2005; all rights reserved.
Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer
1 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA, 2 Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA, 3 Department of Medicine, Massachusetts General Hospital, Boston, MA 02115, USA, 4 Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA and 5 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
* To whom correspondence should be addressed at: 44 Binney Street, Room 822, Smith Building, Boston, MA 02115, USA. Tel: +1 617 632 5632; Fax: +1 617 632 3709; Email: penelope_miron{at}dfci.harvard.edu
Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The NMU breast cancer model induced in the rat is used for the study of mammary carcinogenesis because it closely mimics human breast disease. To assess the validity of this model from a more global molecular perspective, and also to devise a general technique to compare animal profiles with human microarray studies, we have characterized 25 NMU-induced mammary tumors and 11 normal glands using a combination of immunohistochemical and microarray analyses. The rat mammary carcinomas were classified as non-invasive, ER-positive ductal carcinomas with a composition of differentiated epithelial and myoepithelial cell lineages. Gene expression profiles generated using rat Affymetrix arrays containing 15 866 genes demonstrated that the rat mammary tumors are homogeneous and that H-ras mutations did not confer a unique molecular signature. We compared the resulting rat profiles with those obtained from a human dataset by merging the raw microarray data, using an approach that involves a combination of cross-species and cross-platform analysis. Using this novel strategy, we demonstrate the ability of 2305 rat orthologs to recapitulate the classification of human tumors derived from human Affymetrix arrays. The gene expression profiles of the NMU-induced primary tumors were most similar to ER-positive, low to intermediate grade breast cancer. Our technique provides a means to correlate gene expression data from animal models of cancer to human cancer and disease states.
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