| First Author | Morisawa T | Year | 2008 |
| Journal | Int J Cancer | Volume | 123 |
| Issue | 12 | Pages | 2735-40 |
| PubMed ID | 18781563 | Mgi Jnum | J:141272 |
| Mgi Id | MGI:3817837 | Doi | 10.1002/ijc.23853 |
| Citation | Morisawa T, et al. (2008) Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression. Int J Cancer 123(12):2735-2740 |
| abstractText | Various molecular changes characterizing organ-specific carcinogenesis have been identified in human tumors; however, the molecular mechanisms of the genomic changes specific for each cancer are not well defined. A transgenic (Tg) mouse model with constitutive expression of the nucleotide-editing enzyme, activation-induced cytidine deaminase (AID), develops tumors in various organs as a result of the mutagenic activities of AID. This phenotypic character of AID Tg mice allowed us to analyze the organ-specific genetic changes in tumor-related genes commonly triggered by AID-mediated mutagenesis. Among the 80 AID Tg mice analyzed, 11 mice developed hepatocellular carcinomas, and 7 developed lung cancers. In addition, 1 developed the gastric cancer and 3 developed gastric adenomas. Organ-specific preferences for nucleotide changes were observed in some of the tumor-related genes in each epithelial tissue of the AID Tg mice. Of note, the c-myc and K-ras genes were the preferential targets of the mutagenic activity of AID in lung and stomach cancers, respectively, whereas mutations in the p53 and beta-catenin genes were commonly observed in all 3 organs. Quantitative RT-PCR analyses revealed that alpha-fetoprotein, insulin-like growth factor2 and cyclin D1 genes were specifically upregulated in HCC, whereas upregulation of the matrix metalloproteinase7 gene was more marked in lung cancer. Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ-specific genetic diversity in oncogenic pathways during cancer development. (c) 2008 Wiley-Liss, Inc. |
