Proliferation of cultured human prostate cancer cells is inhibited by insulin-like growth factor (IGF) binding protein-1: evidence for an IGF-II autocrine growth loop.
In this study, we examined the expression of insulin-like growth factor (IGF) ligands, receptors, (IGFR1, IGFR2), and binding proteins (IGFBPs) in the human prostate cancer cell line DU145, as well as its mitogenic response to the IGFs. Using RNase protection assays, we found expression of IGF-II, IGFR1, and IGFR2 but failed to detect IGF-I messenger RNA. Distinct binding protein species as well as immunoreactive IGF-II were detected in conditioned media using radioligand and immunoblotting assays. Compared with controls, treatment with exogenous IGF-I and IGF-II resulted in stimulation of monolayer and anchorage-independent growth. Recombinant human IGFBP-1, which binds IGF-II with high affinity, inhibited IGF-II-induced monolayer growth and both baseline and IGF-II-induced anchorage-independent growth in this cell line. Our data suggest IGF-II is as an autocrine growth factor in DU145 cells, and that inhibition of IGF-II-dependent growth of human prostate cancer cells may represent a new therapeutic strategy for this disease.
Figueroa
J A
JA
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7884, USA.
Lee
A V
AV
Jackson
J G
JG
Yee
D
D
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000235:genetics; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D007335:Insulin-Like Growth Factor II