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Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells
- Source :
- Vrije Universiteit Brussel
- Publication Year :
- 2009
-
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). Design 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. Conclusion 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.
- Subjects :
- Male
Serum
medicine.medical_specialty
Serum/metabolism
Receptor, IGF Type 1/antagonists & inhibitors
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
proliferation
Prostatic Neoplasms/pathology
Biology
Receptor, IGF Type 1
Cell Proliferation/drug effects
Prostate cancer
Endocrinology
DU145
Internal medicine
Cell Line, Tumor
LNCaP
Antibodies, Blocking/pharmacology
medicine
Humans
Insulin-Like Growth Factor I
Receptor
Antibodies, Blocking
Protein Kinase Inhibitors
PI3K/AKT/mTOR pathway
Cell Proliferation
Medicine(all)
DNA synthesis
Dose-Response Relationship, Drug
Growth factor
apoptosis
Prostatic Neoplasms
medicine.disease
IGF-I
Insulin-Like Growth Factor I/metabolism
Protein Kinase Inhibitors/pharmacology
Cancer research
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 15322238
- Volume :
- 21
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Growth hormoneIGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
- Accession number :
- edsair.doi.dedup.....770bf3b5bdeb140f35bc821b821ee45a