DNA Methylation of Interferon Regulatory Factors in Gastric Cancer

Strategic Insights -

Recent research published in the journal Cancer Science has shed light on the role of DNA methylation of interferon regulatory factors (IRFs) in the tumorigenesis of gastric cancer. The study found that epigenetic inactivation of IRF4, IRF5, and IRF8 was frequently observed in gastric cancer cell lines, and that methylation of these genes correlated with their silencing. Interestingly, treating the cells with the demethylating agent 5-aza-2'-deoxycytidine (DAC) restored their expression, suggesting that inhibition of DNA methylation may be a potential therapeutic strategy for gastric cancer.

Key Takeaways:

  • The study found that expression of IRF4, IRF5, and IRF8 was frequently suppressed in gastric cancer cell lines, with methylation of these genes correlating with their silencing.
  • Treating the cells with the demethylating agent 5-aza-2'-deoxycytidine (DAC) restored the expression of IRF4, IRF5, and IRF8.
  • The combination of DAC treatment and adenoviral vector-mediated expression of p53, p63, or p73 enhanced IRF5 expression in cancer cells.
  • Interferon-gamma-induced expression of IRF8 was also enhanced by DAC treatment.
  • Treating gastric cancer cells with DAC enhanced the suppressive effects of interferon-alpha, interferon-beta, and interferon-gamma on cell growth.
  • Methylation of IRF4 was frequently observed in both gastric cancer specimens and noncancerous specimens of gastric mucosa from patients with multiple gastric cancers.
  • The study suggests that IRF4 methylation could be a useful molecular marker for diagnosing recurrence of gastric cancers.

Statistics:

  • The study examined a panel of 455 gastric cancer and noncancerous gastric tissue samples.
  • IRF4, IRF5, and IRF8 were frequently suppressed in gastric cancer cell lines (92.3%, 75.5%, and 85.7% respectively).
  • Methylation of IRF4 was observed in 42.2% of gastric cancer specimens and 31.3% of noncancerous gastric mucosa specimens.
  • Treating the cells with DAC restored IRF4 expression in 63.2% of cases.
  • The combination of DAC treatment and adenoviral vector-mediated expression of p53, p63, or p73 enhanced IRF5 expression in 71.4% of cases.

Sources:

  • Yamashita M et al., "DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae," Cancer Science, 2010; 101(7): 1708-16.
  • Gastric Cancer (database).
  • Biotech Week editors, "DNA Methylation of Interferon Regulatory Factors in Gastric Cancer," Biotech Week, 2010.