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.
Ma
Yu
Y
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Lu
Bingjian
B
Ruan
Wenjing
W
Wang
Hongqiang
H
Lin
Jie
J
Hu
Hu
H
Deng
Hong
H
Huang
Qiong
Q
Lai
Maode
M
D000375:Aging / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000737:chemistry; D016147:Genes, Tumor Suppressor; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
D017077:Culture Media, Conditioned; D018969:Insulin-Like Growth Factor Binding Proteins; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase