Silencing of phosphoinositide-specific phospholipase C ε remodulates the expression of the phosphoinositide signal transduction pathway in human osteosarcoma cell lines

Anticancer Res. 2014 Aug;34(8):4069-75.

Abstract

Background: Ezrin, a member of the ezrin-radixin-moesin family, is involved in the metastatic spread of osteosarcoma. Ezrin binds phosphatydil inositol-4,5-bisphosphate (PIP2), a crucial molecule of the phosphoinositide signal transduction pathway. PIP2 levels are regulated by phosphoinositide-specific phospholipase C (PI-PLC) enzymes. PI-PLCε isoform, a well-characterized direct effector of rat sarcoma (RAS), is at a unique convergence point for the broad range of signaling pathways that promote RAS GTPase-mediated signalling.

Materials and methods: By using molecular biology methods and microscopic analyses, we analyzed the expression of ezrin and PLC genes after silencing of PLCE (OMIM *608414) in 143B and Hs888 cell lines.

Results: The growth rate of the cells was slowed, and the expression of ezrin, PLCB1, PLCG2 and PLCD4 was significantly modified. Ezrin displacement from the plasma membrane was observed.

Conclusion: The present results corroborate the hypothesis that ezrin and the PI signal transduction system are involved in a common network.

Keywords: Osteosarcoma; ezrin; gene silencing; phosphoinositides; phospholipase c; plce; signal transduction.

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Phosphatidylinositols / physiology*
  • Phosphoinositide Phospholipase C / analysis
  • Phosphoinositide Phospholipase C / genetics
  • Phosphoinositide Phospholipase C / physiology*
  • Phospholipase C beta / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*

Substances

  • Cytoskeletal Proteins
  • Phosphatidylinositols
  • ezrin
  • PLCB1 protein, human
  • Phosphoinositide Phospholipase C
  • Phospholipase C beta
  • phospholipase C epsilon