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(American Journal of Pathology. 2006;168:597-607.)
© 2006 American Society for Investigative Pathology

CSR1 Suppresses Tumor Growth and Metastasis of Prostate Cancer

Guoying Yu*, George C. Tseng{dagger}, Yan Ping Yu*, Tim Gavel*, Joel Nelson{ddagger}, Alan Wells*, George Michalopoulos*, Demetrius Kokkinakis*§ and Jian-Hua Luo*

From the Departments of Pathology* and Urology,{ddagger} the Center of Biostatistics,{dagger} and the Hillman Cancer Center,§ University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

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.




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