Differential expression of molecular markers in arsenic- and non-arsenic-related urothelial cancer

Background: Little is known about the mechanisms of arsenic-related urothelial cancer (AsUC). The aim of this study was to reveal the differential expression of molecular markers between AsUC and non-arsenic-related UC (non-AsUC). Materials and Methods: Tissues of AsUC (n=33), non-AsUC (n=20) and normal bladder urothelia from patients with benign diseases (n=4) were examined for multiple selected molecular markers responsible for various cellular functions, including glutathione, GST-π, Bcl-2, p53 and c-Fos. Results: The mean cellular glutathione content of normal mucosal samples (33.4±7.2 μM/mg protein) was significantly higher than either non-AsUC (22.8±1.8, p=0.04) or AsUC (16.4±1.6, p=0.002). The glutathione content of non-AsUC was higher than that of AsUC (p=0.012). The expressions of Bcl-2 and c-Fos in AsUC were significantly higher than those in non-AsUC (p=0.004 and p=0.02, respectively). Conclusion: The carcinogenic pathway for AsUC is different, in part, from that of non-AsUC. Cellular glutathione contents may be down-regulated during urothelial carcinogenesis. Bcl-2 and c-Fos may play important roles in arsenic-mediated carcinogenesis of the urothelium.