High expression of Cdc25B and low expression of 14-3-3σ is associated with the development and poor prognosis in urothelial carcinoma of bladder.

Cdc25 dual-specicity phosphatases are essential regulators at critical stages of cell cycle. Cdc25B is overexpressed in several human tumor types. The activity of Cdc25B is regulated by 14-3-3 dimer. To investigate the roles of Cdc25B and 14-3-3σ in bladder carcinoma, we examined expressions of Cdc25B and 14-3-3σ proteins in bladder carcinoma and cell lines and analyzed their roles in the development and prognosis of urinary bladder carcinoma. Immunohistochmistry was used to detect the expressions of Cdc25B and 14-3-3σ in 105 bladder carcinomas. Moreover, expressions of Cdc25B and 14-3-3σ were analyzed by real-time PCR and Western blot in 40 bladder carcinomas and 20 normal epithelial tissues. Specific siRNA was used to knockdown the expression of Cdc25B or 14-3-3σ. Wild-type plasmid was used to overexpress 14-3-3σ. MTT assay and Flow cytometry were used to examine proliferation and cell cycle of bladder cancer cells. There were higher Cdc25B expression and lower 14-3-3σ expression in carcinomas than in the adjacent normal tissues (P < 0.05), positive and negative correlations being noted with clinical stage and histopathologic grade. Cdc25B expression was positively correlated with recurrence and poor prognosis. Downregulation of Cdc25B resulted in slower growth, more G2/M cells and 14-3-3σ increasing. However, upregulation and downregulation of 14-3-3σ did not affect cell growth and Cdc25B expression. It showed that Cdc25B upregulation and 14-3-3σ downregulation might promote development of bladder cancer and suggested a poor prognosis. Moreover, Cdc25B could play an important role on the bladder cancer cell proliferation and cell cycle progression and regulate expression of 14-3-3σ.