| Project/Area Number |
23791847
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | AED / 子宮体癌 / MDM2 / PCR-SSCP |
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| Research Abstract |
#1. To search the AEDs of human MDM2gene, we analyzed 45 samples from the endometrial cancer patients and the healthy controls by PCR-SSCP-based method. Out of 20 endometrial cancer patients, we identified two cases presenting AED. (fig.1) #2. We confirmed that these AED derived from P2 promotor of MDM2gene. And we found new SNP (T/C) on the 5’-upstream of the SNP309 in the MDM2P2 promotor. We found that this SNP created an NF-・B consensus sequence in the Sp1 binding sequence. #3. Using the Chromatin Immunoprecipitation (ChIP) and the luciferase reported assays, we confirmed that the NF-・B consensus sequence formedby the newly-discovered SNP(C-allele) bound to NF-・B, but not T-allele, and that NF-・B can suppress the transcription of MDM2gene. #4. Immnohistochemistry analysis showed that NF-・??p50 protein accumulated in the nuclei of the AED-positive endometrial cancer tissue. #5. The Biacore analysis revealed that p50 preferred C-allele to T-allele, conversely, Sp1 T-allele to C-allele. We also found that they bound to the same DNA region in a competitive manner.
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