PMID:
     16823849
Authors:
     Guo M, House MG, Akiyama Y, Qi Y, Capagna D, Harmon J,
     Baylin SB, Brock MV, Herman JG.
Title:
     Hypermethylation of the GATA gene family in esophageal cancer.
Journal:
     Int J Cancer. 2006 Nov 1;119(9):2078-83. doi: 10.1002/ijc.22092.
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.

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