ERK5 positively regulates cigarette smoke-induced urocystic epithelial-mesenchymal transition in SV‑40 immortalized human urothelial cells

Geng,Hao; Zhao,Li; Liang,Zhaofeng; Zhang,Zhiqiang; Xie,Dongdong; Bi,Liangkuan; Wang,Yi; Zhang,Tao; Cheng,Lei; Yu,Dexin; Zhong,Caiyun

doi:10.3892/or.2015.4130

ERK5 positively regulates cigarette smoke-induced urocystic epithelial-mesenchymal transition in SV‑40 immortalized human urothelial cells

Authors:
- Hao Geng
- Li Zhao
- Zhaofeng Liang
- Zhiqiang Zhang
- Dongdong Xie
- Liangkuan Bi
- Yi Wang
- Tao Zhang
- Lei Cheng
- Dexin Yu
- Caiyun Zhong
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Affiliations: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: July 14, 2015 https://doi.org/10.3892/or.2015.4130
Pages: 1581-1588

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Abstract

Bladder cancer is universally acknowledged as a significant public health issue. Abundant evidence shows that cigarette smoke (CS) is the primary risk factor for bladder cancer. However, the mechanism of CS-induced bladder cancer has not been fully elucidated. CS-induced epithelial-mesenchymal transition (EMT) is critically involved in cell malignant transformation. The role of ERK5, the lesser studied member of the MAPK family, in regulating CS-triggered EMT has not yet been investigated. The objective of the present study was to investigate the regulatory role of ERK5 in CS-induced urocystic EMT. SV-40 immortalized normal human urothelial cells (SV-HUC-1) were used as in vitro CS exposure models. EMT phenotypic alterations were assessed by changes in cell morphology, invasive capacity, as well as expression of epithelial and mesenchymal markers. Protein and mRNA expression levels were analyzed by western blotting and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). ERK5 inhibition studies were performed with a specific inhibitor. Exposure of SV-HUC-1 cells to CS induced morphological change, enhanced invasive capacity, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 positively regulated CS-mediated EMT in urothelial cells, as evidenced by the findings that CS promoted ERK5 activation, and that the CS-triggered alteration in the EMT phenotype was reversed by ERK5 inhibition.

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