2007 Fiscal Year Final Research Report Summary
Study of ovarian carcinogenesis using mice models
| Project/Area Number |
18591847
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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 |
Obstetrics and gynecology
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| Research Institution | Showa University |
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Principal Investigator |
OKUDA Tsuyoshi Showa University, Obstetrics and Gynecology, Researcher (60407434)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Nobuya Hokkaido University, 獣医学研究科, Associate professor (20302614)
MAEDE Shin Asahi Life Foundation, The Institute for Adult Diseases, researcher (40415956)
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| Project Period (FY) |
2006 – 2007
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| Keywords | ovarian carcinoma / beta cathenine / K-ras / OGP promoter / Cre recombinase / model mouse |
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| Research Abstract |
Overall aim : Define the role that multiple genetic change s and inflammation plays in promoting ovarian tumorigenesis.
Specific aim : 1) Establish the mice model system in ovary.2) Determine the role of K-ras and beta-cathenine in the development of mice model of ovarian cancer.3) Determine how NF-kappa B activation pathway influence to the development of ovarian cancer in mammalian system.
Study design: 1. Construction of mutant rake model of K-ras and beta-cathenine in ovary.
1) Construction of ovarian specific Cre recombinase TG mouse. 2) Construction of latent K-ras TG and beta-cathenine TG mouse. 3) Construction of ovarian specific K-ras TG and beta-cathenine TG mouse. 4) Determination of phenotype in mice.
2.Construction of NF kappa B KO and overexpression system in mice ovary.
1)Construction of ovarian specific NF kappaB KO mouse.2)Construction of ovarian specific NF kappaB overexpression mouse.3)Determination of phenotype in mice.
Result 1. Mouse ovarian specific promoter (OGP promo
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ter) was cloned upstream of Cre recombinase gene and transferred into pBS SK(+). The DNA construct was injected into mouse embryo. Three positive strains were obtained and examined to determine the ovarian specific expression of Cre recombinase. At present, the positive expression is not obtained. 2)Mutant exon of beta-cathenine was cloned and placed downstream of CAG promoter, loxP , CAT and loxP sequence and transferred into pBS SK(+).The DNA construct was injected into mouse embryo. One of a strain expressed sutuffer neo in ovary. Using an adeno virus gene delivery technique for the introduction of Cre recombinase into mouse ovary, beta-cat TG was revealed to express cre recombinase in ovarian cells. This system will be used until OGP-Cre system is established. Mutant exon of K-ras was cloned and placed downstream of CAG promote, loxP , CAT and loxP sequence and transferred into pBS SK(+).The DNA construct was injected into mouse embryo.2.Adeno-Cre was injected into the maw oflKKbeta KO mouse. After the confirmation of IKKbeta deletion in ovary phenotyping analysis will be evaluated. Less
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