The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma

J Pathol. 2009 Feb;217(3):345-52. doi: 10.1002/path.2487.

Abstract

A micro-array analysis using biopsies from patients with EBV-positive undifferentiated nasopharyngeal carcinoma (NPC) and from cancer-free controls revealed down-regulation of tumour suppressor genes (TSG) not previously associated with this disease; one such gene was the ataxia telangiectasia mutated (ATM) gene. Q-PCR confirmed down-regulation of ATM mRNA and ATM protein expression in tumour cells was weak or absent in almost all cases. In NPC cell lines, however, ATM was down-regulated only in the EBV-positive line, C666.1, and in none of five EBV-negative lines. In vitro infection of EBV-negative NPC cell lines with a recombinant EBV was followed by the down-regulation of ATM mRNA and protein, and only EBV-positive cells showed a defective DNA damage response following gamma-irradiation. Our data suggest that loss of ATM function could be an important step in the pathogenesis of NPC, and may have implications for the treatment of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / virology
  • Ataxia Telangiectasia Mutated Proteins
  • Case-Control Studies
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • Down-Regulation*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Gene Expression Regulation, Viral*
  • Herpesvirus 4, Human
  • Humans
  • Immunohistochemistry
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / virology
  • Oligonucleotide Array Sequence Analysis
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics*
  • Tumor Virus Infections / complications
  • Tumor Virus Infections / genetics

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases