Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells

Eddy Himpe, Saranyapin Potikanond, Peggy Verdood, Ron Kooijman

Onderzoeksoutput: Articlepeer review

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)252-259
Aantal pagina's8
TijdschriftGrowth Hormone & IGF Research
Volume21
Nummer van het tijdschrift5
DOI's
StatusPublished - 2011

Bibliografische nota

Copyright © 2011 Elsevier Ltd. All rights reserved.

Vingerafdruk

Duik in de onderzoeksthema's van 'Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells'. Samen vormen ze een unieke vingerafdruk.

Citeer dit