CSR1 Suppresses Tumor Growth and Metastasis of prostate cancer

Background Although prostate cancer is frequent among men over 45 years of age, it generally only becomes lethal with metastasis. In this study, we identified a gene, called cellular stress response 1 (CSR1), which was frequently down‐regulated and methylated in prostate cancer samples. Methods We examined the protein expression of CSR1 in 343 prostate samples including 133 normal and 210 cancerous prostate tissues. In addition, we performed methylation analysis on 58 prostate cancer samples to determine the methylation status of CSR1. Results CSR1 was found to be frequently methylated among prostate cancers that metastasize. CSR1 immunohistochemistry using a prostate tissue array indicated that the level of CSR1 protein was down‐regulated in most of the aggressive prostate cancer cases. Survival analysis indicates that methylation of the CSR1 promoter, and to a lesser extent down‐regulation of CSR1 protein expression, is associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3 resulted in a 2 to 3‐fold decrease in colony formation and a 10‐fold reduction in anchorage‐independent growth. PC3 cells stably expressing CSR1 have an average 3‐fold 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% vs. 31%) and mortality (13% vs. 100%). Conclusion The present findings suggest that CSR1 is a potent tumor suppressor gene.