IGF-1 and hyperglycaemia-induced FOXA1 and IGFBP-2 affect epithelial to mesenchymal transition in prostate epithelial cells.

Localized prostate cancer (PCa) is a manageable disease but for most men with metastatic disease, it is often fatal. A western diet has been linked with PCa progression and hyperglycaemia has been associated with the risk of lethal and fatal prostate cancer. Using PCa cell lines, we examined the impact of IGF-I and glucose on markers of epithelial-to-mesenchymal transition (EMT), migration and invasion.

Hyperglycemia Promotes TMPRSS2-ERG Gene Fusion in Prostate Cancer Cells Upregulating Insulin-Like Growth Factor-Binding Protein-2.

Background: Epidemiologic evidence shows that obesity is associated with a greater risk of aggressive prostate cancer (PCa) and PCa-specific mortality and this is observed mainly in men with the gene fusion. Obesity is often associated with comorbid conditions such as type 2 diabetes and hyperglycemia: we investigated whether some of the exposures associated with disturbed metabolism can also affect the frequency of this gene fusion.

Methods: Fusion was induced in LNCaP PCa cells in normal or high levels of glucose, with or without insulin-like growth factor binding protein-2 (IGFBP-2) silenced or the presence of insulin-like growth factor-1 (IGF-I), insulin, or epidermal growth factor (EGF).