Cigarette smoke extract-induced proliferation of normal human urothelial cells via the MAPK/AP‑1 pathway

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/ol.2016.5407

Cigarette smoke extract-induced proliferation of normal human urothelial cells via the MAPK/AP‑1 pathway

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 Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: November 22, 2016 https://doi.org/10.3892/ol.2016.5407
Pages: 469-475

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Abstract

Bladder cancer (BC) is universally acknowledged as a significant public health issue, worldwide. Numerous studies have demonstrated that cigarette smoke is the primary risk factor for BC. However, the mechanism of cigarette smoke‑induced BC has not been fully elucidated. Sustained epithelial cell hyperplasia has been identified as a preneoplastic lesion during the formation of BC. The aim of the present study was to investigate whether exposure to cigarette smoke extract (CSE) induced proliferation in normal human urothelial SV‑HUC‑1 cells. Furthermore, the role of the mitogen‑activated protein kinase (MAPK)/activator protein‑1 (AP‑1) pathway in the CSE‑induced proliferation of SV‑HUC‑1 cells was also investigated. The present study revealed that the expression of phosphorylated‑extracellular signal regulated protein kinase (ERK)1/2, Jun N‑terminal kinase (JNK) and p38 was significantly increased following exposure to CSE in SV‑HUC‑1 cells. Furthermore, CSE increased the expression of the proliferation markers, cyclin D1 and proliferating cell nuclear antigen. By contrast, CSE attenuated the expression of p21. In addition, the inhibitors of ERK1/2 and JNK reversed the aforementioned effects of CSE. However, p38 inhibition did not reverse CSE‑induced proliferation. In conclusion, the results of the present study demonstrated that exposure to CSE induced proliferation in normal human urothelial cells. Furthermore, the results also indicated that the ERK1/2 and JNK pathways are important for the regulation of proliferation via the AP‑1 proteins.

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