| Project/Area Number |
17591666
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
HYOCHI Nobuhiko Tokyo Medical and Dental University, Department of Urology, Assistant Professor (30275896)
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| Co-Investigator(Kenkyū-buntansha) |
KAGEYAMA Yukio Tokyo Medical and Dental University, Department of Urology, Assistant Professor (10211153)
SUGIYAMA Hiroshi Kyoto University, Department of Physiology, Professor (50183843)
KIHARA Kazunori Tokyo Medical and Dental University, Department of Urology, Professor (40161541)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,410,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | polyamide / prostate cancer / androgen receptor / antiandrogen / 遺伝子変異 / 前立腺癌 / 男性ホルモン / 再燃 |
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| Research Abstract |
Androgen binds to the androgen responsive element of target genes and promotes transcription of them. We synthesized pyrrole imidazole polyamides which specifically bind to the ARE and possibly block effects of androgen. We established an assay system based on reporter assay using human prostate cancer cell line, PC3. Transcription of the prostate speck antigen (PSA) gene evoked by androgen was suppressed in a dose dependent manner by some polyamides. However, specificity of the suppressive effects was not significant. Then we focused on mutant androgen receptors identified in clinical samples. We developed three mutant androgen receptors, T877A, W741C, and T877A+W741C. Effects of sterdal and non-steroidal antiandrogens on transcriptional activity of these mutant androgen receptors., Bicalutamide is effective for T877A (resistant to hydroxyflutamide). W741C (resistant to bicalutamide) was suppressed by nilutamide or hydroxyflutamide. Nilutamide and cyproterone acetate showed modest suppression of W741C+T877A. The results were published in the prestigious journal, the Prostate. Base o these results, we are planning to develop novel polyamides effective for mutant androgen receptors.
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