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Hepatic Temporal Gene Expression Profiling in Helicobacter hepaticus-Infected A/JCr MiceDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA, Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Computational and Systems Biology Initiative, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Whitehead Institute For Biomedical Research, Cambridge, Massachusetts 02139, USA
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA, jgfox@ mit.edu Helicobacter hepaticus infection of A/JCr mice is a model of infectious liver cancer. We monitored hepatic global gene expression profiles in H. hepaticus infected and control male A/JCr mice at 3 months, 6 months, and 1 year of age using an Affymetrix-based oligonucleotide microarray platform on the premise that a specific genetic expression signature at isolated time points would be indicative of disease status. Model based expression index comparisons generated by dChip yielded consistent profiles of differential gene expression for H. hepaticus infected male mice with progressive liver disease versus uninfected control mice within each age group. Linear discriminant analysis and principal component analysis allowed segregation of mice based on combined age and lesion status, or age alone. Up-regulation of putative tumor markers correlated with advancing hepatocellular dysplasia. Transcriptionally down-regulated genes in mice with liver lesions included those related to peroxisome proliferator, fatty acid, and steroid metabolism pathways. In conclusion, transcriptional profiling of hepatic genes documented gene expression signatures in the livers of H. hepaticus infected male A/JCr mice with chronic progressive hepatitis and preneoplastic liver lesions, complemented the histopathological diagnosis, and suggested molecular targets for the monitoring and intervention of disease progression prior to the onset of hepatocellular neoplasia.
Key Words: Microarray • hepatitis • chronic • carcinoma • hepatocellular • mice • inbred • Helicobacter.
Toxicologic Pathology, Vol. 32, No. 6,
678-693 (2004) This article has been cited by other articles:
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