CSR1 suppresses tumor growth and metastasis of prostate cancer

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / prevention & control*
  • Adenocarcinoma / secondary*
  • Animals
  • Colony-Forming Units Assay
  • CpG Islands
  • DNA Methylation
  • Heat-Shock Proteins / physiology*
  • Humans
  • Immunoglobulin G / immunology
  • Male
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness / prevention & control
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / prevention & control
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / prevention & control*
  • Rabbits
  • Radiation Tolerance
  • Scavenger Receptors, Class A / physiology*
  • Survival Rate
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Heat-Shock Proteins
  • Immunoglobulin G
  • Peptide Fragments
  • SCARA3 protein, human
  • Scavenger Receptors, Class A