MAPK/AP‑1 pathway regulates benzidine‑induced cell proliferation through the control of cell cycle in human normal bladder epithelial cells

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Abstract

Bladder cancer is the most common malignancy of the urinary tract. Long-term exposure to benzidine is one of the major causes of bladder cancer. However, the mechanism of benzidine‑induced bladder cancer is not yet sufficiently characterized. Dysregulated cell proliferation serves a critical role in cancer initiation and development; whether benzidine promotes cell proliferation, and the role of MAPKs in this process, have not previously been investigated. The present study aimed to investigate the benzidine-induced modulation of intracellular mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) signaling cascades on cell proliferation in SV-40 immortalized human uroepithelial cells (SV‑HUC‑1). It was identified that benzidine exposure enhanced the proliferation of SV-HUC-1 cells, promoted the transition of cells from G1 to S phase and altered the expression level of cell cycle-associated genes at the mRNA and protein levels. Furthermore, exposure of the SV-HUC-1 cells to benzidine was associated with the activation of MAPKs, including extracellular regulated protein kinases 1 and 2, p38 and Jun N-terminal kinase. The downstream target of MAPKs, AP-1 monomers, was also activated. Benzidine-induced proliferation was reversed by MAPK‑specific inhibitors. Thus, the present study demonstrated that benzidine enhances the proliferation of bladder cells via activating the MAPK/AP-1 pathway, which may provide novel insights into the molecular mechanisms of benzidine-initiated bladder tumorigenesis, as well as cancer prevention.

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APA

Zhao, L., Zhang, T., Geng, H., Liu, Z. Q., Liang, Z. F., Zhang, Z. Q., … Zhong, C. Y. (2018). MAPK/AP‑1 pathway regulates benzidine‑induced cell proliferation through the control of cell cycle in human normal bladder epithelial cells. Oncology Letters, 16(4), 4628–4634. https://doi.org/10.3892/ol.2018.9155

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