Genistein affects androgen-responsive genes through both androgen- and estrogen-induced signaling pathways
Genistein affects androgen-responsive genes through both androgen- and estrogen-induced signaling pathways
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DOI：
10.1002/mc.20153
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发表时间：
2006-01-01
影响因子：
4.6
通讯作者：
Wang, TTY
中科院分区：
文献类型：
--
作者：
Takahashi, Y;Hursting, SD;Wang, TTY
这项研究探讨了前列腺癌化学预防药物金雀异黄素调节人前列腺癌LNCaP细胞基因表达的机制。在存在或不存在激素刺激和存在或不存在金雀异黄素的情况下，检测雄激素和雌激素调节基因在LNCaP细胞中的表达。金雀异黄素强烈抑制雄激素反应基因(ARG)mRNAs的基础表达，包括前列腺特异性抗原(PSA)和Ste20相关的丙氨酸氨基转移酶(SPAK)。然而，金雀异黄素对另外两个ARG的基础表达几乎没有影响，即β(2)-微球蛋白(B2M)或硒蛋白P(SEPP1)。在合成雄激素R1881存在的情况下培养LNCaP细胞，可诱导PSA、Spak、B2M和SEPP1 mRNA水平的增加。染料木素均能阻断R1881诱导的这些基因的表达。对于PSA和Spak，金雀异黄素还阻断或下调17β-雌二醇诱导的mRNA表达增加。这些结果表明，金雀异黄素通过调节雄激素和雌激素诱导的信号通路，选择性地改变LNCaP细胞中ARG mRNAs的表达。2005年出版，Wiley-Liss，Inc.
This study examined the mechanisms by which the prostate cancer chemopreventive agent genistein modulates gene expression in LNCaP human prostate cancer cells. Expression of androgen- and estrogen-regulated genes was measured in LNCaP cells cultured in the presence or absence of hormonal stimulation and the presence or absence of genistein. Genistein strongly suppressed basal expression of androgen-responsive gene (ARG) mRNAs, including prostate-specific antigen (PSA) and Ste20-related proline-alanine-rich kinase (SPAK). However, genistein had little or no effect on basal expression of two other ARGs, beta(2)-Microglobulin (B2M) or selenoprotein P (SEPP1). Culturing LNCaP cells in the presence of the synthetic androgen R1881-induced increases in PSA, SPAK, B2M, and SEPP1 mRNA levels. The R1881-induced expression of these genes was uniformly blocked by genistein. For PSA and SPAK, genistein also blocked or downregulated 17 beta-estradiol-induced increases in mRNA expression. These results indicate that genistein selectively alters expression of ARG mRNAs in LNCaP cells through modulation of both androgen- and estrogen-induced signaling pathways. Published 2005 Wiley-Liss, Inc.