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Expression profiling and identification of novel genes in hepatocellular carcinomas

Abstract

Liver cancer is the fifth most common cancer worldwide and unlike certain other cancers, such as colon cancer, a mutational model has not yet been developed. We have performed gene expression profiling of normal and neoplastic livers in C3H/HeJ mice treated with diethylnitrosamine. Using oligonucleotide microarrays, we compared gene expression in liver tumors to three different states of the normal liver: quiescent adult, regenerating adult, and newborn. Although each comparison revealed hundreds of differentially expressed genes, only 22 genes were found to be deregulated in the tumors in all three comparisons. Three of these genes were examined in human hepatocellular carcinomas and were found to be upregulated. As a second method of analysis, we used Representational Difference Analysis (RDA) to clone mRNA fragments differentially expressed in liver tumors versus regenerating livers. We cloned several novel mRNAs that are differentially regulated in murine liver tumors. Here we report the sequence of a novel cDNA whose expression is upregulated in both murine and human hepatocellular carcinomas. Our results suggest that DEN-treated mice provide an excellent model for human hepatocellular carcinomas.

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Acknowledgements

The authors thank J Messamore, E Perguson, S Bartley, Z Diaz, E Lukas and E Armstrong for technical assistance; G Kennedy for the HepG2 cells; J Menetski for collaborative efforts; and the Farnham lab and M Ryan for helpful discussions and critical review of the manuscript. We also thank Dr T Warner and the National Disease Research Interchange for the human tissues. This work was supported in part by research grants from National Cancer Institute/National Institutes of Health CA22484 and National Institute of General Medical Sciences/National Institutes of Health GM08349.

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Graveel, C., Jatkoe, T., Madore, S. et al. Expression profiling and identification of novel genes in hepatocellular carcinomas. Oncogene 20, 2704–2712 (2001). https://doi.org/10.1038/sj.onc.1204391

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