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

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. (C) 2008 Elsevier Inc. All rights reserved.