Jaworski Maike, Ittrich Carina, Hailfinger Stephan, Bonin Michael, Buchmann Albrecht, Schwarz Michael, Köhle Christoph
Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
Int J Cancer. 2007 Sep 15;121(6):1382-5. doi: 10.1002/ijc.22801.
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.
化学诱导的小鼠肝肿瘤在不同的癌基因中存在突变。约50%的肿瘤含有Ha-ras基因的激活突变，约20%的肿瘤显示B-raf癌基因的点突变。我们通过微阵列分析研究了这两种基因型肿瘤中的基因表达谱。相对于正常肝组织，肿瘤中总共约有500个基因或表达序列异常表达。其中约三分之二在Ha-ras和B-raf突变的肝肿瘤中均有显著改变，其余大多数基因在两种肿瘤类型中至少显示出定性可比的变化。在这两种基因型的肿瘤中推测出了几个功能簇，其中涉及一系列编码脂质代谢酶的基因的改变。Ha-ras和B-raf突变的肝肿瘤整体基因表达模式的相似性表明，这两种癌基因的突变激活导致了一组共同的转录调节因子的激活。
