title: Benzidine induces epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway.
abstract: Prolonged benzidine exposure is a known cause of urothelial carcinoma (UC). Benzidine-induced epithelial-to-mesenchymal transition (EMT) is critically involved in cell malignant transformation. The role of ERK1/2 in regulating benzidine-triggered EMT has not been investigated. This study was to investigate the regulatory role of ERK1/2 in benzidine-induced EMT. By using wound healing and transwell chamber migration assays, we found that benzidine could increase SV-HUC-1 cells invasion activity, western blotting and Immunofluorescence showed that the expression levels of Snail, β-catenin, Vimentin, and MMP-2 were significantly increased, while, the expression levels of E-cadherin, ZO-1 were decreased. To further demonstrate the mechanism in this process, we found that the phosphorylation of ERK1/2, p38, JNK and AP-1 proteins were significantly enhanced compared to the control group (*P < 0.05). Afterward, treated with MAPK pathways inhibitors, only ERK inhibitor（U0126）could reduce the expression of EMT markers in SV-HUC-1 cells, but not p38 and JNK inhibitor（SB203580, SP600125）, which indicated that benzidine induces the epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway. Taken together, findings from this study could provide into the molecular mechanisms by which benzidine exerts its bladder-cancer-promoting effect as well as its target intervention.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Liang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China. Electronic address: yudx_urology@126.com.
authors.forename: De-Xin
authors.initials: DX
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: cyzhong@njmu.edu.cn.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Zhong
mesh_terms: D001483:Base Sequence; D001560:Benzidines / Q000494:pharmacology*; D002460:Cell Line; D017931:DNA Primers; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019459:Urothelium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
chemical_list: D001560:Benzidines; D017931:DNA Primers; C029876:benzidine
keywords: Benzidine; ERK1/2 pathway; Epithelial–mesenchymal transition; SV-HUC-1 cells