Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of Health Sciences, Rockville, MD, USA.
Cancer Biol Ther. 2011 Feb 15;11(4):410-7. doi: 10.4161/cbt.11.4.14180.
Androgen dependent induction of the ETS related gene (ERG) expression in more than half of all prostate cancers results from gene fusions involving regulatory sequence of androgen regulated genes (i.e. TMPRSS2, SLC45A3 and NDRG1) and protein coding sequence of the ERG. Emerging studies in experimental models underscore the functions of ERG in prostate tumorigenesis. However, biological and biochemical functions of ERG in prostate cancer (CaP) remain to be elucidated. This study suggests that ERG activation plays a role in prostaglandin signaling because knockdown of ERG expression in TMPRSS2-ERG fusion containing CaP cells leads to altered levels of the 15-hydroxy-prostaglandin dehydrogenase (HPGD), a tumor suppressor and prostaglandin catabolizing enzyme, and prostaglandin E2 (PGE2) . We demonstrate that HPGD expression is regulated by the binding of the ERG protein to the core promoter of this gene. Moreover, prostaglandin E2 dependent cell growth and urokinase-type plasminogen activator (uPA) expression are also affected by ERG knockdown. Together, these data imply that the ERG oncoprotein in CaP cells positively influence prostaglandin mediated signaling, which may contribute to tumor progression.
雄激素依赖性诱导超过一半的前列腺癌中 ETS 相关基因（ERG）的表达，是由于涉及雄激素调节基因（即 TMPRSS2、SLC45A3 和 NDRG1）的调节序列和 ERG 的蛋白编码序列的基因融合所致。在实验模型中的新兴研究强调了 ERG 在前列腺肿瘤发生中的作用。然而，ERG 在前列腺癌（CaP）中的生物学和生化功能仍有待阐明。本研究表明，ERG 激活在前列腺素信号转导中发挥作用，因为在含有 TMPRSS2-ERG 融合的 CaP 细胞中敲低 ERG 表达会导致 15-羟基前列腺素脱氢酶（HPGD）的水平改变，HPGD 是一种肿瘤抑制因子和前列腺素分解代谢酶，以及前列腺素 E2（PGE2）。我们证明，HPGD 表达受 ERG 蛋白与该基因核心启动子结合的调节。此外，前列腺素 E2 依赖性细胞生长和尿激酶型纤溶酶原激活物（uPA）表达也受 ERG 敲低的影响。这些数据表明，CaP 细胞中的 ERG 癌蛋白正向影响前列腺素介导的信号转导，这可能有助于肿瘤进展。
