ATTENUATION OF IGF-I RECEPTOR SIGNALLING INHIBITS SERUM-INDUCED PROLIFERATION OF PROSTATE CANCER CELLS

Objective: Several studies showed that high serum levels of insulin-like growth factor-I (IGF-I) correlate with an increased risk for prostate cancer, although the causal role of IGF-I remains to be established. In this study, we addressed the role of IGF-I as a serum factor on the growth of two androgen-independent cell lines (Du145 and PC3) and one androgen-dependent cell line (LNCaP).

Design: We investigated the effects of a blocking antibody against the IGF-I receptor (?IR3) on DNA synthesis in prostate cancer cells cultured in the presence of recombinant human IGF-I or normal human serum (NHS).

Results: We show that in all three prostate cancer cell lines, NHS exerts a markedly stronger stimulating effect on DNA synthesis than IGF-I, and that the effect of NHS can be completely abrogated by an antibody against the IGF-I receptor (?IR3). Using pharmacological inhibitors of the two canonical IGF-I receptor signalling pathways, we show that the phosphatidylinositol-3'-kinase (PI3K) and the MAPK pathway are not required for the stimulating effect of NHS.

Conclusion: Our observations indicate that the stimulating effect of NHS is completely dependent on IGF-I receptor signalling transduction and that IGF-I stimulates DNA synthesis in prostate cancer cells in strong synergy with other serum factors. We speculate that the role of other serum factors could explain the discrepancy between the results observed in different animal models to study the function of IGF-I in prostate cancer.