Background: In addition to its normal spectrum of metabolic effects, insulin has been identified as a growth factor capable of promoting mitogenic activities. Thus, hyperinsulinemia, a consequence of insulin resistance, is regarded as a potential risk factor for the development of cancer in patients with diabetes. However, the mechanism of action of insulin in prostate cancer has not yet been completely elucidated. The aim of this study was to investigate whether insulin can directly induce mitogenic activity in prostate cancer-derived cell lines and to evaluate the role of the insulin receptor (IR) in mediating this activity.
Methods: A number of prostate cancer cell lines (LNCaP, P69, C4-2 and PC3), representing early and advanced stages of the disease, were employed. Insulin doses ranged between 0 and 500 ng/ml. Insulin-stimulated proliferation rates were measured by hemocytometer cell counting and MTT assay. Cell-cycle dynamics were evaluated by propidium iodide staining and FACS analysis. Activation of the IR was assessed by immunoprecipitation assays. Expression levels of the receptor were measured by western immunoblotting.
Results: Insulin induced cell proliferation in a dose-dependent fashion in the LNCaP and C4-2 cell lines, but not in P69 or PC3 lines. Cell cycle analyses showed that insulin can positively influence LNCaP and C4-2 lines to progress towards the G2/M phase. Immunoprecipitation assays show that in all of the cell lines expressing the IR, insulin activates IR but not IGF1R.
Conclusion: In the model studied, insulin exhibited direct mitogenic activities mediated exclusively through the IR. Further research is needed to fully dissect the molecular mechanism underlying the biological actions of insulin in prostate cancer.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology