| Project/Area Number |
15591673
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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 |
FUJII Yasuhisa Tokyo Medical and Dental University, Medical Hospital, Assistant Professor, 医学部・附属病院, 講師 (70282754)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Satoru Tokyo Medical and Dental University, Medical Hospital, Associate Professor, 医学部・附属病院, 講師 (80313261)
MASUDA Hitoshi Tokyo Medical and Dental University, Graduate School, Clinical Associate, 大学院・医歯学総合研究科, 助手 (60323680)
KIHARA Kazunori Tokyo Medical and Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (40161541)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | activin / prostate specific antigen / prostate cancer / glucocorticoid / renal cancer / vascular endothelial growth factor / prostate specific antigen / prostate / PSA / LNCaP |
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| Research Abstract |
Activins are multifunctional growth and differentiation factors, and stimulate follicle-stimulating hormone (FSH)-β gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. Activin/follistatin system is present in the prostate tissue. Prostate specific antigen (PSA) plays an important role in male reproductive physiology as well as is very important as a tumor marker for prostate cancer. Thus, the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor, and PSA. LNCaP cells were treated with activin A, 5α-dihydrotestosterone (DHT) with or without their antagonists (follistatin, or nonsteroidal antiandrogen bicalutamide). Activin
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A decreased cell growth of LNCaP cells in a dose-dependent manner while DHT increased in a biphasic manner. In contrast to their opposing actions on the cell growth, both activin A and DHT up-regulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, while those of DHT were prevented by bicalutamide, not by follistatin. Activin A up-regulates PSA production and the effect is through androgen receptor independent pathway. Activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to up-regulate PSA in vivo.
Further, in another experiment, we have shown that glucocorticoids, at concentrations achievable in vivo by oral administration of low doses of DEX, have an inhibitory effect on vascular endothelical growth factor (VEGF) mRNA expression and protein secretion of RCC cells possibly through the glucocorticoid receptor pathway. Less
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