CSR1 suppresses tumor growth and metastasis of prostate cancer
CSR1 suppresses tumor growth and metastasis of prostate cancer
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DOI：
10.2353/ajpath.2006.050620
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发表时间：
2006-02-01
影响因子：
6
通讯作者：
Luo, JH
中科院分区：
文献类型：
--
作者：
Yu, GY;Tseng, GC;Luo, JH
前列腺癌在45岁以上的男性中很常见，但通常只有在转移的情况下才会变得致命。在这项研究中，我们发现了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和甲基化。生存分析表明，CSR1启动子的甲基化和CSR1蛋白表达的轻微下调与前列腺癌的高转移率有关。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2-3倍，非锚定生长减少10倍。稳定表达CSR1的PC3细胞体外侵袭能力平均下降三倍。在PC3细胞异种移植中表达CSR1使肿瘤大小、侵袭率(0vs31%)和死亡率(13vs100%)显著减少(gt；8倍)。本研究结果提示，CSR1基因是一种有效的肿瘤抑制基因。
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 suppressor gene.