Tumor suppressor gene insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) induces senescence-like growth arrest in colorectal cancer cells

Exp Mol Pathol. 2008 Oct;85(2):141-5. doi: 10.1016/j.yexmp.2008.04.005. Epub 2008 May 11.

Abstract

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor suppressor gene. This study attempted to explore a potential senescence-like role for IGFBP-rP1 in suppressing human colorectal cancer. Recombinant IGFBP-rP1 inhibited cell proliferation and induced G1 cell cycle arrest in RKO and CW2 cells. It induced a senescence-like phenotype by showing 2-fold higher beta-galactosidase activity in IGFBP-rP1-transfectants over that in control cells. Western blot confirmed down-regulation of phosphorylated retinoblastoma protein (pRB) and up-regulation of p53 in IGFBP-rP1-transfectants as compared with control cells. Thus, IGFBP-rP1 might be a key molecule in the cellular senescence pathway. Our results uncovered a novel molecular mechanism involving the altered expression of pRB and p53 for tumor suppressor gene IGFBP-rP1 in colorectal cancer. Restoration of IGFBP-rP1 function might have potential therapeutic significance in colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Culture Media, Conditioned / chemistry
  • Genes, Tumor Suppressor*
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Insulin-Like Growth Factor Binding Proteins / physiology*
  • Recombinant Fusion Proteins / physiology
  • Transfection
  • beta-Galactosidase / metabolism

Substances

  • Culture Media, Conditioned
  • Insulin-Like Growth Factor Binding Proteins
  • Recombinant Fusion Proteins
  • beta-Galactosidase