INTRODUCTION
Type 2 Diabetes mellitus (DM) is chronic, a metabolic disease that has been associated with an increased risk of cancers including, pancreas, breast, lung, kidney, liver1-5. The association between diabetes and prostate cancer risk has been studied in several epidemiologic studies9-11. Some studies6-8 reported that prostate cancer had been inversely correlated with type 2 DM due to suppressed hypothalamic-pituitary-testicular axis. Otherwise, fewer population-based cohort studies indicated that history of diabetes mellitus was associated with an increased incidence of advanced prostate cancer related to high circulating levels of insulin, insulin resistance, or oxidative stress12-14.
Glycation is the non-enzymatic reaction between reducing sugars, such as glucose and proteins, lipids, or nucleic acids15. The formation of glycation products called AGE is a complicated process involving simple and more complex multistep reactions16. Endogenous formation of AGE can occur through three different pathways, including Maillard reactions, Polyol pathways, and lipid peroxidation17. Elevated levels of glucose accelerate the formation of AGEs. AGEs via their cognate receptor- the AGE specific receptor (RAGE)- can generate reactive oxygen species, activate inflammation signaling cascades and consequently play the role of development of diabetic complications18. AGE enhances several cancer cells by activating the cell cycle proteins (e.g., cyclin D1), anti-apoptotic proteins (e.g., BCL2) and they can contribute to development much cancer including gastric cancer, breast cancer, melanoma, pancreatic cancer and prostate cancer19-23.
To represent the potentially complex relationship between type 2 DM and prostate cancer, we aimed to examine RAGE expression in localize and metastatic prostate cancer by using immunohistochemistry (IHC).