Prohibitin in the pathogenesis of transitional cell bladder cancer.

Our profiling experiment demonstrated that prohibitin 1 (PHB) was ubiquitously expressed in uroepithelial and urothelial carcinoma cell lines and exhibited a trend toward a positive relationship with tumor progression. The aim of this study was, therefore, to examine the potential role of PHB in multistage bladder carcinogenesis and predicting patient outcome. Immunohistochemical staining showed that PHB was overexpressed in 141 out of 167 cases (84.4%) of bladder cancer. This expression was positively related to met receptor overexpression (p = 0.04) and to multiple tumors (p = 0.05). Independent factors in predicting patient survival were multiple tumors (p = 0.002), muscle invasion (p = 0.003), and met overexpression (p = 0.05) in a multivariate analysis. Interestingly, patients with superficial bladder cancer overexpressing both PHB and met had a significantly lower recurrence-free survival rate than those not expressing PHB (p = 0.04). Taken together, our findings showed that PHB was activated at an early stage of carcinogenesis and that it may play a synergistic role with met in the progression of human bladder cancer. In addition, we demonstrated that genistein and justicidin A, natural chemoprevention agents, could suppress the expression of PHB in vitro. Thus, targeting PHB would be a useful approach for treating and preventing human bladder cancer.