| Project/Area Number |
15390491
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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 |
Urology
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| Research Institution | Okayama University |
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Principal Investigator |
NASU Yasutomo Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237572)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masahiro Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (90116509)
KUMON Hiromi Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30144760)
HOH Nanho Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (70173573)
EBARA Shin Okayama University, University Hospital of Medicine and Dentistry, Assistant, 医学部・歯学部附属病院, 助手 (70379741)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | REIC / DKK / Apoptosis / Renal cancer / Prostate cancer / JNK / Bax / Adenovirus / 前立腺癌 / 精巣腫瘍 / 遺伝子治療 / 腎細胞癌 / 膀胱癌 |
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| Research Abstract |
We examined the expression of REIC/Dkk-3, a possible candidate for a tumor suppressor gene, in human renal clear cell carcinoma (RCCC) cell lines and sporadic RCCC surgical specimens. The decreased expression of REIC/Dkk-3 mRNA and protein in human RCCC cell lines (Caki-1,Caki-2,ACHN and KPK-1) were confirmed. Western blot analysis and immunohistochemistry revealed a significant decrease in REIC/Dkk-3 protein levels in 6 of the 7 and 13 of the 14 RCCC cases analyzed, respectively. Thus, REIC/Dkk-3 could be a new molecular target for therapeutic measures against RCCC (J.Urol.171:1314-18,2004).
We also demonstrated that expression of REIC/Dkk-3 was consistently reduced in human prostate cancer tissues in a stage-dependent manner. Forced expression of REIC/Dkk-3 induced apoptosis in human prostate cancer cell lines lacking endogenous REIC/Dkk-3 expression but not in REIC/Dkk-3-proficient normal prostate epithelial and stromal cells. The apoptosis involved JNK activation, mitochondrial translocation of Bax, and reduction of Bcl-2. A single injection of an adenovirus vector carrying REIC/Dkk-3 showed a dramatic anti-tumor effect on a xenotransplanted human prostate cancer. Thus, REIC/Dkk-3 could be a novel target for gene-based therapy of prostate cancer (Cancer Res, 65:9617-9622,2005).
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