| Project/Area Number |
16390460
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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 | Nihon University (2005-2006)
The University of Tokyo (2004) |
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Principal Investigator |
TAKAHASHI Satoru Nihon University School of Medicine, Professor, 医学部, 教授 (50197141)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Satoshi Tokyo University Faculty of Medicine, Professor, 医学部附属病院, 教授 (40251251)
URANO Tomohiko Tokyo University Faculty of Medicine, Assistant, 医学部附属病院, 助手 (20334386)
KUME Haruki Tokyo University Faculty of Medicine, Assistant professor, 医学部附属病院, 講師 (10272577)
MATSUMOTO Shinya Tokyo University Faculty of Medicine, Assistant, 医学部附属病院, 助手 (50345196)
吉田 利夫 日本大学, 医学部, 助教授 (60210704)
平野 大作 日本大学, 医学部, 講師 (40228804)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | estrogen / estrogen receptor / EBAG9 / 14-3-3σ / prostate / estrogen-related receptor / CYP2B6 / androgen / 前立腺 / CAR / CYP3A4 / ERR / efp |
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| Research Abstract |
We investigated hormonal pathways involving in cell proliferation of prostatic epithelium and cancer. We especially focused on the roles of estrogen receptors (ERs)α ＆ β, and a newly identified estrogen responsive gene; EBAG 9. We found a positive role of ERα in cancer cell proliferation, which is mediated by increased EBAG 9 expression and down-regulation of 14-3-3a. In contrast, ERβ showed suppressive effects on cancer cell proliferation and progression. Decreased or lost expression of ERβ significantly correlated with advanced pathological stages and higher Gleason scores, even poor prognosis. Recently identified estrogen-related receptor (ERR) α was found to be often down-regulated in prostate cancer, and a negative predictor for patient prognosis. We also identified crucial roles of not only testosterone, but also its metabolite for prostatic cell proliferation and cancer progression. Cytochrome P450 2B6 (CYP2B6), which plays an important role in the degeneration of testosterone, was found to be down-regulated in prostatic cancer tissue. CYP2B6 is likely to be regulated by ERRα and constitutive androstane receptor (CAR), and a prognostic factor of prostatic cancer.
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