Interaction between endogenous mutator AID and exogenous oncogenic factors in carcinogenesis
| Project/Area Number |
16390115
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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 | Kyoto University |
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Principal Investigator |
KINOSHITA Kazuo Kyoto University, Graduate School of Medicine, Research Associate Professor, 医学研究科, 科学技術振興助教授 (50293874)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | mutation / somatic hypermutation / class-switch recombination / AID / Cre recombinase / エストロゲン受容体融合タンパク |
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| Research Abstract |
Exogenous chemical substance and physical factors have long been considered to be primary causes of genetic mutations associated with cancer development. However, such view is still hypothetical and lacks good experimental support. On the contrary, there is emerging hypothesis that cancer develops as a consequence of interaction between endogenous mutators and exogenous agents. Activation-induced cytidine deaminase (AID) is one of endogenous mutators. Overexpression of AID in mice causes T-cell lymphoma and lung cancer. Study of oncogenic potential of AID in other organs of this mouse model is difficult due to early death from T-cell lymphoma. To circumvent this problem, new transgenic model was created, in which temporal and spatial control of AID expression is made possible using Cre-loxP recombination system. Expression of Cre regulated by tissue-specific promoters induces excision of green fluorescent protein-coding element and expression of downstream AID gene. Such conditional AID transgenic mice (AID cTg) were crossed with CD19-Cre and TNAP-Cre mice, resulting in B cell-specific and systemically mosaic expression, respectively. Unexpectedly, B cell-specific AID expression did not cause B-cell tumor, suggesting negative regulation of overexpressed AID activity in B cells. Mosaic expression of AID caused liver and lung tumor in some individuals at 60 weeks after birth. This result suggests potential tumorigenicity of AID in other organs than T cells and lung.
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression2005
Author(s)
Kotani, A., Okazaki, I.M., M., Muramatsu, M., Kinoshita, K., Begum, N.A., Nakajima, T., Saito, H., Honjo, T.
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Journal Title
Proc.Natl.Acad.Sci.U.S.A. 102
Pages: 4506-4511
Related Report
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[Journal Article] Separate domains of AID are required for somatic hypermutation and class-switch recombination2004
Author(s)
Shinkura, R., Ito, S., Begum, N.A., Nagaoka, H., Muramatsu, M., Kinoshita, K., Sakakibara, Y., Hijikata, H., Honjo, T.
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Journal Title
Nat.Immunol. 5
Pages: 707-712
Related Report
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[Journal Article] Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch2004
Author(s)
Begum, N.A., Kinoshita, K., Kakazu, N., Muramatsu, M., Nagaoka, H., Shinkura, R., Biniszkiewicz, D., Boyer, L.A., Jaenisch, R., Honjo, T.
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Journal Title
Science 305
Pages: 1160-1163
Related Report
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[Journal Article] De novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination2004
Author(s)
Begum, N.A., Kinoshita, K., Muramatsu, M., Nagaoka, H., Shinkura, R., Honjo, T.
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Journal Title
Proc.Natl.Acad.Sci.U.S.A. 101
Pages: 13003-13007
Related Report
