Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells.
Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells.
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DOI：
10.1371/journal.pone.0021417
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sreekumar A
中科院分区：
文献类型：
--
作者：
Putluri N;Shojaie A;Vasu VT;Nalluri S;Vareed SK;Putluri V;Vivekanandan-Giri A;Byun J;Pennathur S;Sana TR;Fischer SM;Palapattu GS;Creighton CJ;Michailidis G;Sreekumar A
前列腺癌是美国男性癌症相关死亡的第二大原因。临床局限性前列腺癌的发生和进展高度依赖于雄激素信号传导。转移性肿瘤最初对抗雄激素治疗有反应，但在进展时对该方案产生耐药性。基因组学和蛋白质组学研究表明雄激素在调节前列腺癌代谢过程中发挥作用。然而，迄今为止还没有进行代谢组学分析研究，研究前列腺癌中雄激素调节的生化过程。在这里，我们使用无偏的代谢组学分析加上富集为基础的生物过程映射，以获得深入了解前列腺癌细胞系中雄激素介导的生化改变。我们的研究结果表明，雄激素暴露导致前列腺癌细胞中氨基酸代谢的升高和甲基化潜力的改变。此外，代谢表型研究证实，在用雄激素治疗的前列腺癌细胞中，通过与氨基酸代谢相关的途径的通量更高。这些发现提供了深入了解前列腺癌中雄激素信号调节的潜在生化过程。在临床上，如果得到验证，这些途径可用于开发补充当前雄激素消融治疗的治疗策略，而观察到的雄激素调节的代谢特征可用作预示去势抵抗性前列腺癌发展的生物标志物。
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.
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