Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.
PLoS One. 2011;6(7):e21417. doi: 10.1371/journal.pone.0021417. Epub 2011 Jul 18.
Prostate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer.
前列腺癌是美国男性癌症相关死亡的第二大主要原因。临床局限性前列腺癌的发展和进展高度依赖雄激素信号。转移性肿瘤最初对抗雄激素治疗有反应，但随着病情的进展，会对该方案产生耐药性。基因组和蛋白质组学研究表明，雄激素在调节前列腺癌中的代谢过程中起作用。然而，迄今为止，还没有进行代谢组学分析研究来检查雄激素调节前列腺癌中的生化过程。在这里，我们使用无偏代谢组学分析结合基于富集的生物过程映射，深入了解雄激素在前列腺癌细胞系中介导的生化改变。我们的研究结果表明，雄激素暴露导致氨基酸代谢升高和前列腺癌细胞甲基化潜力改变。此外，代谢表型研究证实，雄激素处理的前列腺癌细胞中与氨基酸代谢相关的途径通量更高。这些发现为雄激素信号调节前列腺癌的潜在生化过程提供了深入了解。临床上，如果得到验证，这些途径可以被开发用于制定治疗策略，补充当前的去势治疗，而观察到的雄激素调节的代谢特征可以作为预示去势抵抗性前列腺癌发展的生物标志物。
