title: Hypermethylation of the GATA gene family in esophageal cancer.
abstract: 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.
authors.affiliation: Cancer Biology Program, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA.
authors.forename: MingZhou
authors.initials: M
authors.lastname: Guo
authors.forename: Michael G
authors.initials: MG
authors.lastname: House
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
authors.forename: Domenico
authors.initials: D
authors.lastname: Capagna
authors.forename: John
authors.initials: J
authors.lastname: Harmon
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
mesh_terms: D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics*; D050980:GATA Transcription Factors / Q000235:genetics; D050991:GATA4 Transcription Factor / Q000235:genetics*; D050992:GATA5 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D050980:GATA Transcription Factors; D050991:GATA4 Transcription Factor; D050992:GATA5 Transcription Factor