Analysis of molecular mechanism for modification of p53 tumor suppressor protein by anti-cancer drugs
| Project/Area Number |
18580289
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
ARAI Katsuhiko Tokyo University of Agriculture and Technology, Faculty of Agriculture, Associate Professor (60175940)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | tumor suppressor gene / p53 / microtubule / tubulin / cell culture / anti-cancer drug / vinca alkaloid / vincristine / チュブリン |
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| Research Abstract |
The aim of this research project is to obtain the information about the effects of anti-cancer drugs, especially vinca alkaloid, which play as a inhibitor of polymerization of microtubules, on the function of p53 superfamily. Head investigator, K. Arai found that β-tubulin isotypes transformed during establishment of drug-resistance for vinca alkaloid in mouse melanoma cell line, B16F10. Normally, expression of-tubulin expression was suppressed by p53 protein and decrease of DNA binding activity of Sp1 and p53 was induced by addition of vinca alkaloid to the culture medium. In 2006, to examine whether vinca alkaloid affect interaction between p53 superfamily and Sp1, in vitro translation system for p53 superfamily and Sp1 was established. Briefly, full length cDNAs corresponding to transactivating forms for p63, p73 and Sp1 in addition to wild-type and mutated p53 were amplified, then subcloned into pcDNA3.1 or pcDNA3.1/V5-His and used for in vitro transcription/translation. These enable to analyze interaction between p53 superfamily and Sp1 and their kinetics. In 2007, forced expression of p53 superfamily genes in p53-deficient mouse macrophage cell line was designed. Furthermore, mRNA distribution of p53 superfamily in the lung was examined by in situ hybridization and ribonuclease protection assay. As a result, mRNA corresponding to transactivating form of p73 was expressed in bronchial and type II alveolar epithelium. These findings indicated that p73 participate lung carcinogenesis.
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Piperonyl butoxide activates c-Jun and ATF-2 in the hepatocytes of mice.2008
Author(s)
M., Muguruma, K., Arai, M., Moto, J., Nishimura, Y., Dewa, K., Mitsumori
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Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Active Expression of Matrix Metalloproteinase-13 mRNA in the Granulation Tissue of Equine Superficial Digital Flexor Tendinitis.2007
Author(s)
M., Nomura, Y., Hosaka, Y., Kasashima, H., Ueda, K., Takehana, A., Kuwano, K., Arai
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Journal Title
J. Vet. Med. Sci. 69
Pages: 367-369
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gene expression analysis in mice liver on hepatocarcinogenesis by flumequine.2006
Author(s)
Y., Kashida, A., Takahashi, M., Moto, M., Okamura, M., Muguruma, M., Jin, K., Arai, K. Mitsumori
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Journal Title
Arch Toxicol. 9
Pages: 1-7
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of type XII collagen promoter-transgenic mice.2006
Author(s)
Y., Sakai, E., Kubota, T., Nishiyama, M., Shibata, S., Amano, K., Arai
Organizer
142th annual meeting of Japanese Society of Veterinary Medicine
Place of Presentation
Yamaguchi
Year and Date
2006-09-23
Description
「研究成果報告書概要(欧文)」より
Related Report
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