Cigarette Smoke Extract-induced Proliferation of Normal Human Urothelial Cells Via the MAPK/AP-1 Pathway
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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.
Liang Z, Zhang Y, Xu Y, Zhang X, Wang Y Oncol Lett. 2023; 25(1):30.
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High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis.
Aguayo F, Munoz J, Perez-Dominguez F, Carrillo-Beltran D, Oliva C, Calaf G Cancers (Basel). 2020; 12(8).
PMID: 32781676 PMC: 7465661. DOI: 10.3390/cancers12082201.