ERK5 regulates Tobacco smoke-induced urocystic epithelial-mesenchymal transition in BALB/c mice

Abstract

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.