Protein Tyrosine Phosphatase Zeta Enhances Proliferation By Increasing Beta-Catenin Nuclear Expression In Vhl-Inactive Human Renal Cell Carcinoma Cells

We investigated the role of protein tyrosine phosphatase zeta (Ptprz1) in human renal cell carcinoma (RCC) cells' proliferation and associations between Ptprz1 expression and von Hippel-Lindau (VHL) activation.A normal human renal cell line and four human RCC cell lines were used in this study. VHL or Ptprz1 expression in RCC cells was increased by transfection with a VHL or Ptprz1 vector. VHL or Ptprz1 expression was decreased in these cells by siRNA using Lipofectamine 2000. Cells' proliferative activity was assessed by WST-1 assay.Our results suggested that Ptprz1 was a target of VHL, and a loss of VHL activation increased Ptprz1 expression in RCC cells. Ptprz1 enhanced beta-catenin protein expressions in the nuclear fractions of RCC cells and participated in regulating proliferation by activating beta-catenin and its downstream genes. In addition, a loss of VHL activity may enhance the proliferative activity of RCC cells by increasing Ptprz1 expression.Ptprz1-enhanced RCC cells' proliferation depends on VHL inactivation, and the Ptprz1/beta-catenin pathway may be a potential target for treating RCC with inactive VHL.