Insulin-like growth factor I: action and receptor characterization in human prostate cancer cell lines.
The role of insulin-like growth factor I (IGF-I) in the growth and development of prostate cancer was studied using established human prostate cancer cell lines. Under steroid and growth factor-free culture conditions, IGF-I significantly stimulated the androgen-independent cell lines PC-3 and DU-145 to incorporate [3H]thymidine into DNA, while the androgen-dependent cell line, LNCaP, was not affected. However, in the presence of dihydrotestosterone (DHT), DNA synthesis of LNCaP cells was stimulated by IGF-I in a dose-dependent manner. None of the cell lines tested secreted an immunoreactive level of IGF-I into their conditioned medium. Characterization of receptors by ligand binding assays revealed that all prostate cancer cell lines tested express specific binding sites for IGF-I with similar dissociation constants (0.23-0.39 nM). Crosslinking studies supported the suggestion that 125I-IGF-I was bound to a receptor on these cells. The IGF-I receptor concentrations of androgen-independent cell lines were significantly higher than those of the androgen-dependent cell line. Androgen appeared to affect neither the expression of IGF-I receptors nor the secretion of IGF-I. The results suggest that IGF-I may play an important role in stimulating the growth and progression of prostate cancer.
Iwamura
M
M
Department of Urology, University of Rochester, NY 14642-8656.
Sluss
P M
PM
Casamento
J B
JB
Cockett
A T
AT
D001667:Binding, Competitive; D002455:Cell Division / Q000502:physiology; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D017526:Receptor, IGF Type 1 / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D007328:Insulin; D013196:Dihydrotestosterone; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1