PT - JOURNAL ARTICLE AU - Braeuning, Albert AU - Ittrich, Carina AU - Köhle, Christoph AU - Buchmann, Albrecht AU - Schwarz, Michael TI - Zonal Gene Expression in Mouse Liver Resembles Expression Patterns of <em>Ha-ras</em> and β-Catenin Mutated Hepatomas AID - 10.1124/dmd.106.013656 DP - 2007 Apr 01 TA - Drug Metabolism and Disposition PG - 503--507 VI - 35 IP - 4 4099 - http://dmd.aspetjournals.org/content/35/4/503.short 4100 - http://dmd.aspetjournals.org/content/35/4/503.full SO - Drug Metab Dispos2007 Apr 01; 35 AB - Hepatocytes of the periportal and perivenous zones of the liver lobule differ in their levels and activities of various enzymes and other proteins. We have recently suggested that β-catenin- and Ras-dependent signaling pathways play an important role in the regulation of perivenous and periportal gene expression profiles. This hypothesis was primarily based on similarities in zonal differences in gene expression of hepatocytes from normal liver with gene expression patterns of liver tumors: several proteins and mRNAs preferentially expressed in periportal hepatocytes were often overexpressed in Ha-ras mutated mouse liver tumors, whereas perivenous markers were overexpressed in Ctnnb1 (encoding β-catenin) mutated tumors. We have now extended this work by use of data from two previously conducted microarray analyses aimed to analyze 1) global gene expression patterns of Ha-ras and Ctnnb1 mutated mouse liver tumors and 2) transcriptome differences between periportal and perivenous mouse hepatocytes. By comparison of the datasets, 134 genes or expressed sequences were identified that were present in both datasets. Gene expression patterns in perivenous hepatocytes and Ctnnb1 mutated hepatoma cells were strongly correlated: 96.5% of the genes present in both datasets were regulated in the same direction. In analogy, expression of 74.1% of the genes deregulated in Ha-ras mutated tumors was correlated with the respective expression patterns in periportal hepatocytes. These findings favor the hypothesis that gene expression patterns in periportal and perivenous hepatocytes are regulated, at least in part, by Ras- and β-catenin-dependent signaling pathways. The American Society for Pharmacology and Experimental Therapeutics