title: CSR1 suppresses tumor growth and metastasis of prostate cancer.
abstract: 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.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Yu
authors.forename: George C
authors.initials: GC
authors.lastname: Tseng
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Yu
authors.forename: Tim
authors.initials: T
authors.lastname: Gavel
authors.forename: Joel
authors.initials: J
authors.lastname: Nelson
authors.forename: Alan
authors.initials: A
authors.lastname: Wells
authors.forename: George
authors.initials: G
authors.lastname: Michalopoulos
authors.forename: Demetrius
authors.initials: D
authors.lastname: Kokkinakis
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Luo
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control* / Q000556:secondary*; D000818:Animals; D003114:Colony-Forming Units Assay; D018899:CpG Islands; D019175:DNA Methylation; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000517:prevention & control; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D011817:Rabbits; D011836:Radiation Tolerance; D051117:Scavenger Receptors, Class A / Q000502:physiology*; D015996:Survival Rate; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D010446:Peptide Fragments; C112525:SCARA3 protein, human; D051117:Scavenger Receptors, Class A