Insulin-like growth factor binding protein 1 expression inhibits insulin-like growth factor I action in MCF-7 breast cancer cells.
Interactions between insulin-like growth factor I (IGF-I) and the type of I IGF receptor may be affected by high-affinity extracellular binding proteins. To date, six distinct IGF binding proteins (IGFBPs) have been identified, but their physiological roles are not well understood. For example, depending on experimental conditions, IGFBP-1 has been shown to both enhance and inhibit IGF-I mediated mitogenesis. We have previously shown that excess exogenous IGFBP-1 inhibited IGF-I mediated growth of MCF-7 cells. In this study, we examined whether or not endogenously expressed IGFBP-1 could interfere with IGF-I mediated growth of MCF-7 cells. Cells were stably transfected with an IGFBP-1 expression vector. IGFBP-1 mRNA was produced by the cells, and protein was detected in the conditioned media by ligand blot and immunoblot. Type I IGF receptor could not be phosphorylated by IGF-I in cells expressing IGFBP-1; however, an IGF-I analogue (Arg-3-IGF-I), which cannot complex with IGFBPs, stimulated receptor phosphorylation. IGF-I did not stimulate cell growth in IGFBP-1 expressing cells. These results suggest that IGFBP-1 expression in MCF-7 breast cancer cells inhibits IGF-I induced growth by interrupting the interaction between IGF-I and its receptor.
Yee
D
D
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7884.
Jackson
J G
JG
Kozelsky
T W
TW
Figueroa
J A
JA
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D017526:Receptor, IGF Type 1 / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1