Hypermethylation of the GATA gene family in esophageal cancer

Ming Zhou Guo, Michael G. House, Yoshimitsu Akiyama, Yu Qi, Domenico Capagna, John Harmon, Stephen B. Baylin, Malcolm V. Brock, James G. Herman

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2078-2083
Number of pages6
JournalInternational Journal of Cancer
Issue number9
StatePublished - Nov 1 2006


  • Esophageal cancer
  • GATA genes
  • Hypermethylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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