Hypermethylation of the GATA gene family in esophageal cancer

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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2078-2083
Number of pages6
JournalInternational Journal of Cancer
Volume119
Issue number9
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

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Esophageal Neoplasms
Methylation
Cell Line
Genes
decitabine
Genetic Promoter Regions
Squamous Cell Carcinoma
GATA Transcription Factors
Gene Expression
CpG Islands
DNA Methylation
Colonic Neoplasms
Stomach Neoplasms
Embryonic Development
Gastrointestinal Tract
Epithelium
Epithelial Cells
Polymerase Chain Reaction
Neoplasms
Adenocarcinoma Of Esophagus

Keywords

  • Esophageal cancer
  • GATA genes
  • Hypermethylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Guo, M., House, M., Akiyama, Y., Qi, Y., Capagna, D., Harmon, J., ... Herman, J. G. (2006). Hypermethylation of the GATA gene family in esophageal cancer. International Journal of Cancer, 119(9), 2078-2083. https://doi.org/10.1002/ijc.22092

Hypermethylation of the GATA gene family in esophageal cancer. / Guo, MingZhou; House, Michael; Akiyama, Yoshimitsu; Qi, Yu; Capagna, Domenico; Harmon, John; Baylin, Stephen B.; Brock, Malcolm V.; Herman, James G.

In: International Journal of Cancer, Vol. 119, No. 9, 01.11.2006, p. 2078-2083.

Research output: Contribution to journalArticle

Guo, M, House, M, Akiyama, Y, Qi, Y, Capagna, D, Harmon, J, Baylin, SB, Brock, MV & Herman, JG 2006, 'Hypermethylation of the GATA gene family in esophageal cancer', International Journal of Cancer, vol. 119, no. 9, pp. 2078-2083. https://doi.org/10.1002/ijc.22092
Guo, MingZhou ; House, Michael ; Akiyama, Yoshimitsu ; Qi, Yu ; Capagna, Domenico ; Harmon, John ; Baylin, Stephen B. ; Brock, Malcolm V. ; Herman, James G. / Hypermethylation of the GATA gene family in esophageal cancer. In: International Journal of Cancer. 2006 ; Vol. 119, No. 9. pp. 2078-2083.
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