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Toxicologic Pathology
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Articles

Microarray Data Analysis of Mouse Neoplasia

David E. Malarkey1, Joel S. Parker3, Coral A. Turman4, Allyson M. Scott4, Richard S. Paules2, Jennifer Collins2 and Robert R. Maronpot1

1 Laboratory of Experimental Pathology
2 National Cener for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
3 Constella Group, Durham, North Carolina 27707, USA
4 North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27606, USA

Correspondence: Address correspondence to: David E. Malarkey, Laboratory of Experimental Pathology, Maildrop B3-06, National Institute of Environmental Health Sciences, 111 Alexander Dr., P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA; e-mail:malarkey{at}niehs.nih.gov

Microarray gene expression analysis offers great promise to help us understand the molecular events of experimental carcinogenesis, but have such promises been fulfilled? Studies of gene expression profiles of rodent are being published and demonstrate that yes, indeed, gene array data is furthering our understanding of tumor biology. Recent studies have identified differentially expressed genes in rodent mammary, colon, lung, and liver tumors. Although relatively few genes on the rodent arrays have been fully characterized, information has been generated to better identify signatures of histologic type and grade, understand invasion and metastasis, identify candidate biomarkers of early development, identify gene networks in carcinogenesis, understand responses to therapy, and decifer overlap with molecular events in human cancers. Data from mouse lung, mammary gland, and liver tumor studies are reviewed as examples of how to approach and interpret gene array data. Methods of gene array data analysis were also applied for discovery of genes involved in the regression of mouse liver tumors induced by chlordane, a nongenotoxic murine hepatocarcinogen. Promises are beginning to be fulfilled and it is clear that pathologists and toxicologists, in collaboration with molecular biologists, bioinformatists, and other scientists are making great strides in the design, analysis, and interpretation of microarray data for cancer studies.

Key Words: Liver • lung • mammary gland • rodent • microarray gene expression analysis • genomics • cancer • review • gene expression profiling • neoplasia

Abbreviations: GST, glutathione-s-transferase • AFP, alpha fetoprotein • IGFBP1, insulin-like growth factor binding protein 1 • IGF, insulin-like growth factor • MIG, monokine induced by {gamma} interferon • CRG-L1, cancer related gene-liver 1 • Ig, immunoglobulin • Tff3, intestinal trefoil factor 3 • EGFR, epidermal growth factor receptor • TNF, tumor necrosis factor • GSK3β, glycogen synthase kinase 3 beta • T-ag, SV 40 T-antigen • MMTV, mouse mammary tumor virus • DEN, diethylnitrosamine • HCC, hepatocellular carcinoma

Toxicologic Pathology, Vol. 33, No. 1, 127-135 (2005)
DOI: 10.1080/01926230590888315


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