Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer

Biochem Biophys Res Commun. 2004 Jan 30;314(1):223-8. doi: 10.1016/j.bbrc.2003.12.079.


RUNX family transcription factors are integral components of TGF-beta signaling pathways and have been implicated in cell cycle regulation, differentiation, apoptosis, and malignant transformation. It was noted previously that allele loss and loss of expression of RUNX3 are causally involved in gastric carcinogenesis. Our results demonstrate that RUNX3 is inactivated by aberrant DNA methylation in approximately 19% of lung cancer cell lines and 24% of primary lung cancer specimens. RUNX3 methylation is tumor-specific, since it is not observed in surrounding normal lung tissues. Our results suggest that loss of RUNX3 expression by DNA hypermethylation is frequently associated with the evolution of lung cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Core Binding Factor Alpha 3 Subunit
  • CpG Islands / genetics*
  • DNA Methylation*
  • DNA, Neoplasm / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / methods*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Molecular Sequence Data
  • Silencer Elements, Transcriptional / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • Core Binding Factor Alpha 3 Subunit
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Runx3 protein, human
  • Transcription Factors