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 dev elopment of prostate cancer was studied using established human prosta te cancer cell lines. Under steroid and growth factor-free culture con ditions, IGF-I significantly stimulated the androgen-independent cell lines PC-3 and DU-145 to incorporate [H-3]thymidine into DNA, while th e androgen-dependent cell line, LNCaP, was not affected. However, in t he 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 cond itioned 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 I-125-IGF-I w as bound to a receptor on these cells. The IGF-I receptor concentratio ns of androgen-independent cell lines were significantly higher than t hose 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 stimulati ng the growth and progression of prostate cancer.