Proliferation of DU145 prostate cancer cells is inhibited by suppressing insulin-like growth factor binding protein-2.
BACKGROUND
Insulin-like growth factor binding protein-2 (IGFBP-2) is expressed by all human prostate cancer cell lines and dramatically increases in the serum of prostate cancer patients. However, the role of IGFBP-2 in prostatic tumorigenesis is not known. The aim of the present study was to investigate the effects of IGFBP-2 on the proliferation of DU145 human prostate cancer cells in culture.


METHODS
Using cell proliferation assays, we examined the effects of exogenously administered and endogenously modulated levels of IGFBP-2 on the proliferation of DU145 cells.


RESULTS
Cell growth was stimulated by exogenously administered IGFBP-2, but significantly retarded (P < 0.05) by its neutralizing antibody. Overexpression of IGFBP-2 by transfection also stimulated cell growth, which was significantly (P < 0.05) inhibited in transfectants expressing antisense mRNA to IGFBP-2. Furthermore, the proliferation of IGFBP-2 overexpressing cells was significantly dampened by exogenously administered IGFBP-2 antibody.


CONCLUSIONS
IGFBP-2 is an autocrine growth factor for DU145 human prostate cancer cells and cell proliferation can be significantly retarded by neutralizing or inhibiting its synthesis. These findings provide a strong rationale for targeting IGFBP-2 in the testing of novel strategies to treat prostate cancer.
Department of Obstetrics & Gynecology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1069, USA. schakrab@utmb.edu
Shilla
S
Chatterjee
Eun Sung
ES
Park
Melvyn S
MS
Soloff
D002455:Cell Division / Q000187:drug effects; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D018971:Insulin-Like Growth Factor Binding Protein 2