Expression of mismatch repair gene PMS2 in nasopharyngeal carcinoma and regulation by glycogen synthase kinase-3β in vivo and in vitro

Auris Nasus Larynx. 2012 Feb;39(1):71-6. doi: 10.1016/j.anl.2011.02.009. Epub 2011 May 14.

Abstract

Objective: To evaluate the expression of mismatch repair gene PMS2 in human nasopharyngeal carcinoma (NPC) tissues and evaluate the effect of glycogen synthase kinase (GSK)-3β on PMS2 production in vivo and in vitro.

Methods: The expression of PMS2 and inactivated phosphorylated GSK-3β(s9) was examined by immunohistochemical staining in 25 NPC tissues and the relation was determined by correlation analysis. The effect of GSK-3β transfection in CNE-2 cells on PMS2 production as well as cell apoptosis and chemosensitization were evaluated using small interference RNA (siRNA), immunoblotting and flow cytometric analysis in vitro.

Results: The expression of inactivated phosphorylated GSK-3β(s9) was found to negative correlated with PMS2 in vivo. And transfected GSK-3β was found to be able to enhance PMS2 production, and increase cell apoptosis in CNE-2 cells in combination with cisplatin administration in vitro.

Conclusion: Inactivation of GSK-3β might be important for NPC tumorgenesis through negatively regulating PMS2 production, and enhanced PMS2 production by GSK-3β is beneficial for understanding the NPC tumorgenesis and developing potential strategy for future therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Adult
  • Apoptosis / drug effects
  • Carcinoma / genetics*
  • Cell Line, Tumor
  • Cisplatin
  • DNA Mismatch Repair / drug effects
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / physiology*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Loss of Heterozygosity
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Transfection

Substances

  • DNA-Binding Proteins
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • DNA Repair Enzymes
  • Cisplatin