Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells

被引:0
作者
Hidenori Kawashima
Tomoaki Tanaka
Jed-Sian Cheng
Syozo Sugita
Kazuyoshi Ezaki
Takeshi Kurisu
Tatsuya Nakatani
机构
[1] Osaka City University Graduate School of Medicine,Department of Urology
来源
Urological Research | 2004年 / 32卷
关键词
Androgen receptor; Anti-estrogens; Estrogen; Prostate cancer; Estrogen receptors;
D O I
暂无
中图分类号
学科分类号
摘要
Although some anti-estrogens have been reported to inhibit the proliferation of prostate cancer cells, few studies on the mechanism by which they suppress the growth of prostate cancer have been reported. We investigated, for the first time, whether anti-estrogens modulate the transactivation activity of the androgen receptor (AR) in prostate cancer cells. In DU-145 cells transfected with AR, the transactivation activity of AR was inhibited by tamoxifen and toremifene, even in the presence of 10 nM of DHT. On the other hand, in LNCaP cells having an endogenous AR mutation at codon 877, the activity of AR was suppressed by faslodex in the presence of 10 nM DHT, whereas it was not inhibited by tamoxifen nor toremifene. In PC-3 cells, both the cell growth and the AR activity were remarkably inhibited by tamoxifen at 50 μM. Faslodex and toremifene inhibited AR activity to some extent, but they seemed to function as agonists at higher concentrations. In PC-3 cells, the inhibition of cell growth by flutamide, faslodex and toremifene was much less than their suppression of AR activity. We also demonstrated that a synthetic estrogen diethylstilbestrol and progesterone-related drugs such as chlormadinone acetate and allylestrenol dose-dependently inhibited the activity of AR in DU-145 and PC-3 cells. These results highlight the anti-androgenic aspect of anti-estrogens and estrogens in regard to the AR-mediated transcription of the relevant genes in prostate cancer.
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页码:406 / 410
页数:4
相关论文
共 22 条
[1]  
Griffiths undefined(2000)undefined Prostate 45 87-undefined
[2]  
Bonkhoff undefined(1999)undefined Am J Pathol 155 641-undefined
[3]  
Kuiper undefined(1996)undefined Proc Natl Acad Sci U S A 93 5925-undefined
[4]  
Chang undefined(1999)undefined Prostate 40 115-undefined
[5]  
Lau undefined(2000)undefined Cancer Res 60 3175-undefined
[6]  
Latil undefined(2001)undefined Cancer Res 61 1919-undefined
[7]  
Nanni undefined(2002)undefined J Clin Invest 110 219-undefined
[8]  
Raghow undefined(2002)undefined Cancer Res 62 1370-undefined
[9]  
Huynh undefined(2001)undefined J Endocrinol 171 109-undefined
[10]  
Kim undefined(2002)undefined Cancer Res 62 5365-undefined