Upregulation of discoidin domain receptor 2 in nasopharyngeal carcinoma

Head Neck. 2008 Apr;30(4):427-36. doi: 10.1002/hed.20724.

Abstract

Background: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and has high metastatic potential. Discoidin domain receptors (DDR1, DDR2) are receptor-type tyrosine kinases activated by collagen. Their ability to induce expression of matrix metalloproteinase is related with tumor invasion. Therefore, we aim to investigate DDRs gene expression and its regulation in NPC.

Methods and results: By use of real-time quantitative polymerase chain reaction (Q-PCR), DDR2 gene expression but not DDR1 was significantly higher in primary and metastatic NPC. DDR2 was predominantly distributed in NPC tumor cells rather than in infiltrating lymphocytes. EBV Z-transactivator (Zta) transfection may distinctly elevate DDR2 level. Furthermore, data from reporter assay indicate that Zta could transactivate DDR2 promoter activity, suggesting the possible upregulation mechanism.

Conclusion: DDR2 was differentially upregulated in NPC and modulated by EBV Zta protein. DDR2 may play a role in NPC invasion and serve as a diagnostic and therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Discoidin Domain Receptors
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Lymphocytes / metabolism
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Polymerase Chain Reaction
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Mitogen / genetics*
  • Receptors, Mitogen / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Up-Regulation / genetics*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • BZLF1 protein, Herpesvirus 4, Human
  • Receptors, Mitogen
  • Trans-Activators
  • Viral Proteins
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases