| Project/Area Number |
13671683
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
FUJIMOTO Naohiro University of Occupational and Environmental Health, Department of Urology, Associated professor, 医学部, 助教授 (30209100)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Prostate cancer / androgen receptor / cofactor / hormone therapy / 前立腺 |
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| Research Abstract |
Andorgen-hypersensitivity is one of the possible mechanisms by which prostate cancer progresses from androgen-dependent to androgen-independent state. Previously, we established androgen-hypersensitive cells, LN-TR2, by a long term treatment of LNCaP cells with tumor necrosis factor α. Since the nuclear androgen receptor (AR) was increased in LN-TR2 compared to LNCaP cells after androgen stimulation, the increased nuclear AR may contribute to androgen-hypersensitivity. To explore other mechanism of androgen-hypersensitivity of LN-TR2 cells, we examined AR DNA sequence and the expression of AR cofactors.
AR gene sequence in LN-TR2 cells was identical to that in LNCaP. AR gene mutation, therefore, does not contribute to androgen-hypersensitivity of LN-TR2 cells. The expression levels of two AR coactivator, ARA55 and TIF2, were higher in LN-TR2 than in LNCaP cells. Luciferase assay demonstrated that ARA55 can function as an AR coactivator, but TIF 2 effect is little in LNCaP cells. In human prostate tissues, ARA55 was predominantly expressed in benign epithelial and cancer cells compared to stromal cells. Those results suggest that LN-TR2 cells became androgen-hypersensitive by an increase of AR cocativator ARA55 in addition to the increased nuclear AR and that ARA55 is expressed in prostate cancer cells and may contribute to progression to androgen-independent state.
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