A novel role of alkaline phosphatase in the ERK1/2 dephosphorylation in renal cell carcinoma cell lines: a new plausible therapeutic target

Biochimie. 2014 Dec:107 Pt B:406-9. doi: 10.1016/j.biochi.2014.09.016. Epub 2014 Sep 18.

Abstract

Extracellular regulated kinase 1/2 (ERK1/2) has been shown to be activated in renal cell carcinoma (RCC). Previously, we have reported aberrant expression/activity of Liver/Bone/Kidney alkaline phosphatase (L/B/K ALP) in RCC. The present study was conducted to find out whether L/B/K ALP has any role in the dephosphorylation of ERK1/2 in renal cancer cell lines. Two renal cancer cell lines viz. ACHN and A498 were transfected with full length L/B/K ALP cDNA. ALP expression/activity and ERK1/2 phosphorylation were evaluated. Increased L/B/K ALP expression/activity was associated with significantly reduced (P = 0.001) phosphorylation status of ERK1/2 in ALP cDNA transfected cells in comparison to that of control. This is the first study that suggests deactivation of ERK1/2 by stimulation of ALP in renal cancer cell lines which can be used as a therapeutic target of RCC.

Keywords: ERK1/2; L/B/K alkaline phosphatase; Phosphorylation; Transfection.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • DNA, Complementary
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Molecular Targeted Therapy
  • Phosphorylation
  • Transfection

Substances

  • DNA, Complementary
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Alkaline Phosphatase