Hypermethylation of the GATA gene family in esophageal cancer

Int J Cancer. 2006 Nov 1;119(9):2078-83. doi: 10.1002/ijc.22092.


The GATA family of transcription factors promotes the normal development of the gastrointestinal tract during embryogenesis and determines tissue differentiation in adult gut epithelium. Loss of GATA-4 and GATA-5 has been reported in human gastric and colon cancer. We examined GATA-4,-5 and -6 gene expression in established esophageal squamous cancer cell lines and the relationship to DNA methylation in the promoter region of these genes. GATA-4 and GATA-5 expression was absent in most esophageal cancer cell lines, but was restored upon treatment with the demethylating agent 5-aza-2'-deoxycytidine. For each of the cell lines without detectable GATA gene expression, aberrant methylation of the promoter region CpG-island was detected by methylation specific PCR. We confirmed these results with genomic bisulfite sequencing. GATA-6 expression was found in each of the cell lines. GATA-4/-5 promoter methylation was not detected in normal esophageal mucosa, but GATA-4 methylation was present in 27 of 44 (61%) squamous carcinomas and 31 of 44 (71%) adenocarcinoma of the esophagus, while GATA-5 methylation was present in 14 of 44 (32%) squamous carcinomas and 24 of 44 (55%) adenocarcinoma of the esophagus. Our studies demonstrate frequent silencing of GATA-4 and GATA-5, but not GATA-6, in human esophageal neoplasia associated with gene promoter hypermethylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Methylation*
  • DNA Primers
  • DNA, Neoplasm / genetics
  • Esophageal Neoplasms / genetics*
  • GATA Transcription Factors / genetics
  • GATA4 Transcription Factor / genetics*
  • GATA5 Transcription Factor / genetics*
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Multigene Family
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA Primers
  • DNA, Neoplasm
  • GATA Transcription Factors
  • GATA4 Transcription Factor
  • GATA5 Transcription Factor