ZEB1 promotes prostate cancer proliferation and invasion through ERK1/2 signaling pathway

X.-F. Song, H. Chang, Q. Liang, Z.-F. Guo, J.-W. Wu

Department of Urology, Minhang Hospital Affiliated to Fudan University, Shanghai, China. jiawenwus@sina.com

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• Oncology

OBJECTIVE: Prostate cancer is a kind of malignancy with high occurrence in the male urogenital system. However, the mechanism of the occurrence, the progression, and the metastasis of prostate cancer are still unclear. Searching for the effective molecule target is of great significance to improve the curative effect on prostate cancer. Zinc finger E box binding protein-1 (ZEB1) protein is a member of the zinc finger transcription factor family that participates in the embryonic development and formation. ZEB1 was found to be involved in the occurrence and in the development of multiple cancers, while its role in prostate cancer still needs elucidation.

MATERIALS AND METHODS: Normal prostate cell line PC-3M and prostate cancer cell line DU145 were cultured in vitro and transfected by ZEB1 siRNA. ZEB1 mRNA and protein expressions were detected by real-time PCR and Western blot assay. Cell proliferation was determined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration was evaluated by transwell assay. Cell apoptosis was evaluated by caspase-3 activity. The impact of ZEB1 on extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway was assessed by Western blot assay.

RESULTS: ZEB1 expression significantly increased in DU145 cells compared with PC-3M cells (p<0.05). ZEB1 mRNA and protein obviously declined, cell proliferation inhibited, cell invasion suppressed, and Caspase-3 activity enhanced in DU145 cells after ZEB1 siRNA transfection (p<0.05). ZEB1 siRNA markedly decreased ERK1/2 phosphorylation in DU145 cells compared with control (p<0.05).

CONCLUSIONS: Inhibition of ZEB1 promoted prostate cancer apoptosis, restrained proliferation, and suppressed invasion through down-regulating ERK1/2 signaling pathway.

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