title: Cigarette smoke extract-induced proliferation of normal human urothelial cells via the MAPK/AP-1 pathway.
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.
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Liangkuan
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
keywords: bladder cancer; cigarette smoke extract; mitogen-activated protein kinase/activator protein-1 pathway; proliferation