title: Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells.
abstract: 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).
  
  
  METHODS
  We investigated the effects of a blocking antibody against the IGF-I receptor (αIR3) 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 (αIR3). Using pharmacological inhibitors of the two canonical IGF-I receptor signaling pathways, we show that the phosphatidylinositol-3'-kinase (PI3K) and the Mek-Erk pathways are not required for the stimulating effect of NHS.
  
  
  CONCLUSIONS
  Our observations indicate that the stimulating effect of NHS is completely dependent on IGF-I receptor signaling 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.
authors.affiliation: Medical School, Department of Pharmacology, Vrije Universiteit Brussel, Belgium. Ehimpe@gmail.com
authors.forename: Eddy
authors.initials: E
authors.lastname: Himpe
authors.forename: Saranyapin
authors.initials: S
authors.lastname: Potikanond
authors.forename: Peggy
authors.initials: P
authors.lastname: Verdood
authors.forename: Ron
authors.initials: R
authors.lastname: Kooijman
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D044967:Serum / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019138:Antibodies, Blocking; D047428:Protein Kinase Inhibitors; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1