2007 Fiscal Year Final Research Report Summary
Interaction between endogeneous mutator AID and exogenous oncogenic factors in carcinogenesis
| Project/Area Number |
18390122
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Research Institute, Shiga Medical Center |
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Principal Investigator |
KINOSHITA Kazuo Research Institute, Shiga Medical Center, Shiga Medical Center Research Institute, Staff Scientist (50293874)
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| Project Period (FY) |
2006 – 2007
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| Keywords | gene / cancer / genome / mutation |
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| Research Abstract |
Activation-induced cytidine deaminase(AID) is a unique enzyme that can induce mutations in the genome and is an essential factor for somatic hypermutation and class-switch recombination of the immunoglobulin genes. This study revealed that AID was expressed not only in activated B lymphocytes but also in the liver under chronic hepatitis and tissues of hepatocellular carcinoma. AID expression in hepatocytes was upregulated by infection with hepatitis C virus. In the stomach, AID expression was induced in the epithelium by infection with Helicobacter pylori. AID expressed in a gastric cancer cell line could induce point mutations in a tumor suppressor p53 gene. These findings collectively suggested involvement of AID in the pathogenesis of epithelial cancer arising in the background of chronic inflammation and infection. To clarify role of AID in cancer, experiments of chemical-induced carcinogenesis were performed in mice. Initially, we used AID transgenic mice with ubiquitous and constitutive promoter, which were turned out to be unsuitable for the quantitative study because of frequent and early death from lethal lymphoma. The second trial using mice that lack lymphocytes failed due to growth retardation by frequent pneumonia. Therefore, we started the third trial generating a novel line of AID transgenic mice using skin-specific keratin 14 promoter. Obtained mice were backcrossed to FVB/N strain, which is prone to develop skin tumor. The skin tumor induction by chemicals has just begun.
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