Yu Guoying, Tseng George C, Yu Yan Ping, Gavel Tim, Nelson Joel, Wells Alan, Michalopoulos George, Kokkinakis Demetrius, Luo Jian-Hua
Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Am J Pathol. 2006 Feb;168(2):597-607. doi: 10.2353/ajpath.2006.050620.
Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3 resulted in a two- to threefold decrease in colony formation and a 10-fold reduction in anchorage-independent growth. PC3 cells stably expressing CSR1 had an average threefold decrease in their ability to invade in vitro. Expression of CSR1 in PC3 cell xenografts produced a dramatic reduction (>8-fold) in tumor size, rate of invasion (0 versus 31%), and mortality (13 versus 100%). The present findings suggest that CSR1 is a potent tumor sup-pressor gene.
前列腺癌在45岁以上男性中很常见，但通常只有在发生转移时才会致命。在本研究中，我们鉴定出一种名为细胞应激反应1（CSR1）的基因，该基因在前列腺癌样本中经常下调并发生甲基化。生存分析表明，CSR1启动子的甲基化以及CSR1蛋白表达的下调（程度较轻）与前列腺癌转移的高发生率相关。在前列腺癌细胞系DU145和PC3中强制表达CSR1导致集落形成减少两到三倍，非锚定依赖性生长减少10倍。稳定表达CSR1的PC3细胞体外侵袭能力平均降低三倍。在PC3细胞异种移植中表达CSR1可使肿瘤大小、侵袭率（从31%降至0）和死亡率（从100%降至13%）显著降低。目前的研究结果表明，CSR1是一种有效的肿瘤抑制基因。
