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: Li Zhao, Hao Geng, Zhao-Feng Liang, Zhi-Qiang Zhang, Tao Zhang, De-Xin Yu, Cai-Yun Zhong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 459 Issue 4 Pg. 643-9 (Apr 17 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 25757908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Benzidines
• DNA Primers
• benzidine

Topics

• Base Sequence
• Benzidines (pharmacology)
• Cell Line
• DNA Primers
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• MAP Kinase Signaling System
• Reverse Transcriptase Polymerase Chain Reaction
• Urothelium (cytology, drug effects, enzymology)