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

Shikha Bose1, Lee-Fah Yap, Matthew Fung

  • 1Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK.

The Journal of Pathology
|January 15, 2009
PubMed

Insights

Loss of the ataxia telangiectasia mutated (ATM) gene function is linked to nasopharyngeal carcinoma (NPC) development. EBV infection down-regulates ATM, potentially impacting NPC treatment strategies.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Nasopharyngeal carcinoma (NPC) is a complex malignancy with poorly understood pathogenesis.
  • Tumor suppressor genes (TSGs) play a critical role in cancer development and progression.
  • The Epstein-Barr virus (EBV) is implicated in the etiology of NPC.

Purpose of the Study:

  • To identify novel tumor suppressor genes (TSGs) downregulated in EBV-positive undifferentiated nasopharyngeal carcinoma (NPC).
  • To investigate the role of the ataxia telangiectasia mutated (ATM) gene in NPC pathogenesis.
  • To explore the impact of EBV infection on ATM expression and function in NPC.

Main Methods:

  • Microarray analysis of NPC patient biopsies and cancer-free controls.
  • Quantitative PCR (Q-PCR) to confirm ATM mRNA and protein expression.
  • In vitro infection of NPC cell lines with recombinant EBV and subsequent gamma-irradiation assays.

Main Results:

  • Microarray analysis revealed downregulation of previously unassociated TSGs, including ATM, in EBV-positive NPC.
  • Q-PCR confirmed significantly reduced ATM mRNA and protein expression in NPC tumor cells.
  • EBV infection of NPC cell lines led to ATM downregulation and impaired DNA damage response.

Conclusions:

  • Loss of ATM function is a potential key event in the pathogenesis of NPC.
  • EBV-mediated downregulation of ATM may contribute to NPC development.
  • ATM status could have implications for future NPC treatment strategies.

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