Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT)

Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA) were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP).Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15) TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin.Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy.According to the American Cancer Society Cancer Facts & Figures 2008, 68,810 new cases of bladder cancer would have been diagnosed in the United States over the year of 2008, with a total of 14,100 bladder cancer patients dying from the disease. The cost of managing bladder cancer and the associated complications is estimated to be $65,158 per patient per year in the US [1], amounting to a multi-billion dollar economic impact. For bladder cancer patients of all stages, the 5-year survival rate is 80%. For localized disease, the 5-year survival rate is 92%. But the 5-year survival rate sharply declines to 45% and 6% for patients with regional and distant metastasis, respectively. The majority of bladder cancers (90%) are "transitional cell carcinomas" (TCC) [2]. More than 70-80% of the bladder cancers are papil