Global gene expression in Ha-ras and B-raf mutated mouse liver tumors.
Chemically-induced mouse liver tumors harbor mutations in different oncogenes. About 50% of tumors contain activating mutations in the Ha-ras gene contain and about 20% of tumors show point mutations in the B-raf oncogene. We have investigated the gene expression profiles in tumors of the 2 genotypes by microarray analysis. In total, approximately 500 genes or expressed sequences were aberrantly expressed in tumors relative to normal liver tissue. Around two/thirds of them were significantly altered in both Ha-ras and B-raf mutated liver tumors, and most of the remaining genes showed at least qualitatively comparable changes in both tumor types. Several functional clusters were hypothesized in tumors of the 2 genotypes which involve alterations in a battery of genes encoding enzymes of lipid metabolism. The similarity in the patterns of global gene expression of Ha-ras and B-raf mutated liver tumors suggests that mutational activation of the 2 oncogenes results in activation of a common set of transcriptional regulators.
Jaworski
Maike
M
Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
Ittrich
Carina
C
Hailfinger
Stephan
S
Bonin
Michael
M
Buchmann
Albrecht
A
Schwarz
Michael
M
Köhle
Christoph
C
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D004052:Diethylnitrosamine / Q000633:toxicity; D015870:Gene Expression; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000477:Alkylating Agents; D004052:Diethylnitrosamine; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf