2007 Fiscal Year Final Research Report Summary
In vivo model mouse study to examine the effect of alteration of endogenous endocrine status in thyroid tumorigenesis
| Project/Area Number |
18591030
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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 |
Endocrinology
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAMBA Hiroyuki Nagasaki University, Graduate School of Biomedieal Sciences, Associate Professor (80237635)
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| Co-Investigator(Kenkyū-buntansha) |
NORISATO Mitsutake Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor (50404215)
NAKASHINA Masahiro Nagasaki University, Graduate School of Biornedical Sciences, Associate Professor (50284683)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Thyroid cancer / Radiation / Oncogene / Animal Model |
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| Research Abstract |
The aim of the study is to establish transgenic mice that develop thyroid cancer and then to examine the effects of a novel selective nuclear factor kappa B(NF-κB)inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), which change various cytokines status in vivo, in the mouse model.
First Experiment : We prepared two types of transgenic mice. One is BRAF transgenic mice and another is Ret/PTC transgenic mice. Both transgenic mice develop papillary thyroid cancer within 4 weeks after birth. We examined the effect of DHMEQ, which is novel NF-κB inhibitor, to thyroid carcinomas developed in BRAF or RET-transgenic mice in vivo.
Results : Treatment with DHMEQ inhibited NF-κB DNA binding activity and induced apoptosis in dose and time dependent manner in thyroid carcinoma cells in vitro. However, in the in vivo study, DHMEQ could not suppress the NF-κB activity in thyroid carcinomas in the transgenic mice. Through the animal experiments, DHMEQ did not show any side effects in treated mice.
Second Experiment : We tried to establish novel thyroid carcinoma model mice using Cre-Lox-P system, which is allowed to express the interest gene at any time we want. We could establish the double transgenic mice that have Cre gene and BRAF-Lox-P gene. However, the mice could not develop thyroid carcinoma after induction.
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