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).