GATA-4 and GATA-5 Transcription Factor Genes and Potential Downstream Antitumor Target Genes Are Epigenetically Silenced in Colorectal and Gastric Cancer

Yoshimitsu Akiyama, Neil Watkins, Hiromu Suzuki, Kam Wing Jair, Manon Van Engeland, Manel Esteller, Hidekazu Sakai, Chun Yan Ren, Yasuhito Yuasa, James G. Herman, Stephen B. Baylin

Research output: Contribution to journalArticle

Abstract

The GATA family of transcription factors participates in gastrointestinal (GI) development. Increases in GATA-4 and -5 expression occur in differentiation and GATA-6 expression in proliferation in embryonic and adult settings. We now show that in colorectal cancer (CRC) and gastric cancer promoter hypermethylation and transcriptional silencing are frequent for GATA-4 and -5 but are never seen for GATA-6. Potential antitumor target genes upregulated by GATA-4 and -5, the trefoil factors, inhibinα, and disabled-2 (Dab2) are also silenced, in GI cancers, with associated methylation of the promoters. Drug or genetically induced demethylation simultaneously leads to expression, in CRC cells, of all of the GATA-4, -5, and downstream genes. Expression of exogenous GATA-5 overrides methylation at the downstream promoters to activate the target genes. Selection for silencing of both upstream transcription factors and their target genes in GI cancers could indicate that epigenetic silencing of the involved genes provides a summated contribution to tumor progression.

Original languageEnglish (US)
Pages (from-to)8429-8439
Number of pages11
JournalMolecular and cellular biology
Volume23
Issue number23
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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