You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011741 PROLIFERATION AND GLUCOSE METABOLISM IS INFLUENCED DIFFERENTLY BY THE INSULIN-LIKE-GROWTH-FACTOR (IGF)/INSULIN AXIS IN PROSTATE CANCER & BENIGN PROSTATE CELLS Isabel Heidegger, Petra Massoner, and Helmut Klocker Isabel HeideggerIsabel Heidegger Innsbruck, Austria More articles by this author , Petra MassonerPetra Massoner Innsbruck, Austria More articles by this author , and Helmut KlockerHelmut Klocker Innsbruck, Austria More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1710AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Dysregulation and changes in the insulin-like growth factor (IGF) signaling have been related to the pathogenesis and progression of cancer. The IGF1 receptor (IGF1R) is recognized as an attractive target for anticancer therapy (∼65 clinical studies are ongoing). IGF receptors are closely related to insulin receptors (INSRs) and the Metabolic Syndrome represents an important risk factor for prostate cancer (PCa) development and progression. We analyzed the regulation of IGF and insulin receptors upon ligand stimulation and measured the effect on glucose consumption. METHODS mRNA expression levels were analysed using conventional PCR followed by gel electrophoresis(3% Agarose) or by Real Time PCR. Protein levels were determined by Western blot and immunofluorescent staining. Cell proliferation was assessed using 3H-thymidine incorporation assay and cell number counting. Glucose levels were determinated by Gluc Cell Monitoring System™. RESULTS PCa cells (DU 145 and PC3) stimulated by IGF and INS significantly up-regulated both IGF1R and INSR mRNA expression and proteins levels in a reciprocal manner, whereas no change was observed in benign prostate epithelial cells (EP156T, RWPE1). Hence cell proliferation was increased in cancer cell lines upon IGF and INS stimulation, but not in the benign control cell lines. Moreover, we observed that both the IGF1R and the INSR undergo a trans-membrane to nuclear translocation upon growth factor stimulation in cancer cells. Insulin treatment decreased glucose levels in cancer cells, suggesting a negative feedback mechanism. In addition, our experiments show that Actaprid, an insulin analogue commonly used in diabetes therapy, dose dependently increased the IGF1R and INSR levels in PCa cells. CONCLUSIONS This is one of the first projects investigating that both IGF1R and INSR are tightly regulated in prostate cancer. Their expression is influenced by growth factors, culture conditions and reciprocal regulations. Our preliminary data suggest a link between PCa and glucose metabolism. Possibly, for the future glucose measurements in PCa patients may be used as biomarkers for PCa detection or for responsiveness to IGF targeting therapies. In summary, our data provide new insights into the biology of the IGF/INS axis and in the use of IGF1R inhibitors in cancer therapy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e297-e298 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Isabel Heidegger Innsbruck, Austria More articles by this author Petra Massoner Innsbruck, Austria More articles by this author Helmut Klocker Innsbruck, Austria More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...