Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE, USA; Department of Clinical Nursing, School of Nursing, Beijing University of Chinese Medicine, Beijing, P. R. China.
Mol Nutr Food Res. 2013 Oct;57(10):1825-33. doi: 10.1002/mnfr.201200810. Epub 2013 May 10.
Androgen receptor (AR) signaling is critical for all aspects of prostate growth and tumorigenesis. The glucosinolate-derived phenethyl isothiocyanate (PEITC) has recently been demonstrated to reduce the risk of prostate cancer (PCa) and inhibit PCa cell growth. We previously reported that p300/CBP-associated factor (PCAF), a co-regulator for AR, is upregulated in PCa cells through suppression of the mir-17 gene. Here, we assessed the effects of PEITC on PCAF expression and AR-regulated transcriptional activity in PCa cells.
Using AR-responsive LNCaP cells, we observed the inhibitory effects of PEITC on the dihydrotestosterone-stimulated AR transcriptional activity and cell growth of PCa cells. Interestingly, overexpression of PCAF attenuated the inhibitory effects of PEITC on dihydrotestosterone-stimulated AR transcriptional activity. Expression of PCAF was upregulated in PCa cells through suppression of miR-17. PEITC treatment significantly decreased PCAF expression and promoted transcription of miR-17 in LNCaP cells. Functional inhibition of miR-17 attenuated the suppression of PCAF in cells treated by PEITC.
Our results indicate that PEITC inhibits AR-regulated transcriptional activity and cell growth of PCa cells through miR-17-mediated suppression of PCAF, suggesting a new mechanism by which PEITC modulates PCa cell growth.
雄激素受体（AR）信号对前列腺生长和肿瘤发生的各个方面都至关重要。最近有研究表明，芥子油苷衍生的苯乙基异硫氰酸酯（PEITC）可以降低前列腺癌（PCa）的风险并抑制 PCa 细胞生长。我们之前的研究表明，p300/CBP 相关因子（PCAF）是 AR 的共调节因子，通过抑制 mir-17 基因在 PCa 细胞中上调。在这里，我们评估了 PEITC 对 PCa 细胞中 PCAF 表达和 AR 调节的转录活性的影响。
使用 AR 反应性 LNCaP 细胞，我们观察到 PEITC 对二氢睾酮刺激的 AR 转录活性和 PCa 细胞生长的抑制作用。有趣的是，PCAF 的过表达减弱了 PEITC 对二氢睾酮刺激的 AR 转录活性的抑制作用。通过抑制 miR-17，PCAF 在 PCa 细胞中上调。PEITC 处理显著降低 LNCaP 细胞中 PCAF 的表达并促进 miR-17 的转录。miR-17 的功能抑制减弱了 PEITC 处理细胞中 PCAF 的抑制作用。
我们的研究结果表明，PEITC 通过 miR-17 介导的 PCAF 抑制抑制 AR 调节的转录活性和 PCa 细胞的生长，提示 PEITC 调节 PCa 细胞生长的新机制。
Zotero 插件