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

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.

• Authors: Yu Ma, Bingjian Lu, Wenjing Ruan, Hongqiang Wang, Jie Lin, Hu Hu, Hong Deng, Qiong Huang, Maode Lai
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 85 Issue 2 Pg. 141-5 (Oct 2008) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 18701096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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