| Project/Area Number |
11671542
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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 | Kanazawa University |
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Principal Investigator |
KOH Eitetsu Kanazawa university, Department of Urology, Assistant professor, 医学部・附属病院, 助手 (90283134)
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| Co-Investigator(Kenkyū-buntansha) |
NAMIKI Mikio Kanazawa university, Department of Urology, Professor, 医学部, 教授 (70155985)
KOSHIDA Kiyoshi Kanazawa university, Department of Urology, Assistant professor, 医学部・附属病院, 講師 (70186667)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | prostate / cancer / adrenal steroid / glucuronide / LNCaP / PC3 / DU145 / UGT / 前立腺癌 / 副腎ステロイド / 副腎性ステロイド / 硫酸抱合 / コアクチベター |
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| Research Abstract |
Adrenal androgens function as an androgen source within prostate and androgen target tissue. In this study, we compared the ability of three human prostatic cancer cell lines to metabolize the adrenal androgens, dehydroepiandrosterone (DHEA) and androstenedione in living cultured condition. Androgen-independent cell lines PC-3, DU145 and androgen-dependent cell line LNCaP were investigated. The effect of glucuronide and sulfate conjugates was also investigated. There is a strong tendency in PC-3 or DU145 to convert androstenedione to DHEA or DHEA-S reservoir. On the other hand, LNCaP is capable of converting DHEA into androstenedione and subsequently into dihydrotestosterone (DHT). Moreover, androgens were converted into a glucuronide conjugate in LNCaP, but not in PC-3 or DU145. As a result, the metabolism of the adrenal precursor shifted to androgen formation in LNCaP.This could be confirmed by means of reverse transcription-PCR of uridine diphospho-glucuronosyltransferase (UGT) 2B15. Kinetic properties of UGT activity in LNCaP revealed DHT to be a better substrate than testosterone for prostatic UGTs. In conclusion, our findings show that the adrenal precursor pool has the potential to contribute to the regulation of prostatic cells. Moreover, the presence of UGT activities in LNCaP may have a regulatory effect on the active androgen level in the intracellular environment.
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