| Project/Area Number |
12671556
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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 |
Urology
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| Research Institution | Keio University |
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Principal Investigator |
HORIGUCHI Yutaka Keio University, School of Medicine, Instructor, 医学部, 助手 (60229234)
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| Co-Investigator(Kenkyū-buntansha) |
OHKI Takahiro Keio University, School of Medicine, Instructor, 医学部, 助手 (50265948)
NAKASHIMA Jun Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (10167546)
MURAI Masaru Keio University, School of Medicine, Professor, 医学部, 教授 (90101956)
橘 政昭 東京医科大学, 医学部, 教授 (70129526)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | enhancer / gene therapy / liposome / promotor / prostate cancer / suicide gene therapy / targeting / tissue-specific / ターゲティング / 特異的プロモーター |
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| Research Abstract |
For advanced stage of prostate cancers, androgen ablation is the standard choice of treatment and initially it is effective for the majority of patients. However, once cancer becomes relapsed and refractory to androgen ablation therapy, there is no clear consensus of treatments that overcome this disease. Thus, various gene therapies against prostate cancer, especially in a tissue-specific manner, are currently being widely investigated.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein predominantly expressed on human neoplastic prostate epithelial cells. For the development of targeting gene therapy, we are investigating a tissue-specific promoter of PSMA gene. A 1244bp DNA fragment consisted of 5'-flanking region of PSMA gene was cloned into a luciferase reporter plasmid. In PSMA producing LNCaP human prostate cancer cell line, putative PSMA promoter activity was approximately 40% of that of the SV40 promoter/enhancer and it was inversely increased with androgen depletion. While, in other non-PSMA producing prostate and non-prostate cancer cell lines, the promoter activity was not higher than 11% of its control and independent to the androgen concentration. Further evaluation with its deletion constructs revealed possible negative regulatory elements in the PSMA promoter. These unique features of the PSMA promoter in contrast to the prostate-specific antigen promoter will be potentially useful for targeting gene therapy against PSMA producing prostate cancers.
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