ERK5 regulates tobacco smoke‑induced urocystic epithelial‑mesenchymal transition in BALB/c mice.

Tobacco smoke (TS) is an important risk factor of bladder cancer. Epithelial‑mesenchymal transition (EMT) is involved in the initiation and development of cancer. The role of extracellular signal‑regulated kinase (ERK) 5 in regulating TS‑induced EMT remains to be elucidated. The aim of the present study was to investigate the regulatory role of ERK5 in TS‑triggered EMT in the bladder of mice. BALB/c mice were used for an in vivo TS exposure model. Mice were treated for 6 h a day for 12 weeks. The results demonstrated that mice exposed to TS had decreased mRNA and protein expression levels of the epithelial markers E‑cadherin and zonula occludens‑1, whereas expression levels of the mesenchymal markers Vimentin and N‑cadherin were increased. Treatment with XMD8‑92, a highly specific ERK5 inhibitor, effectively abrogated TS‑triggered activation of ERK5, activator protein‑1 and EMT alterations in the bladder of BALB/c mice. The data suggested that ERK5 regulates TS‑mediated urocystic EMT. These findings provide insight into the molecular mechanisms of TS‑associated bladder tumorigenesis.