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PMID: 14612389 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer.

Molecular and cellular biology ·Vol. 23 ·No. 23 ·2003-12-00 ·Pages 8429-39

Akiyama Y, Watkins N, Suzuki H, Jair KW, van Engeland M, Esteller M, Sakai H, Ren CY, Yuasa Y, Herman JG, Baylin SB

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, inhibinalpha, 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.

MeSH Terms
Cell Line, Tumor Colorectal Neoplasms/etiology,genetics CpG Islands DNA Methylation DNA, Neoplasm/genetics DNA-Binding Proteins/genetics Epigenesis, Genetic GATA4 Transcription Factor GATA5 Transcription Factor GATA6 Transcription Factor Gene Silencing Humans Oncogenes Promoter Regions, Genetic Stomach Neoplasms/etiology,genetics Transcription Factors/genetics
Chemicals
DNA, Neoplasm DNA-Binding Proteins GATA4 Transcription Factor GATA5 Transcription Factor GATA5 protein, human GATA6 Transcription Factor GATA6 protein, human Transcription Factors
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Akiyama Yoshimitsu
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Watkins Neil
Suzuki Hiromu
Jair Kam-Wing
van Engeland Manon
Esteller Manel
Sakai Hidekazu
Ren Chun-Yan
Yuasa Yasuhito
Herman James G
Baylin Stephen B
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44 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.23.8429-8439.2003
Published
2003-12-00
Pages
8429-39
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC262684
Subset
IM
Grants
NIEHS NIH HHS · ESO11858 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.23.8429-8439.2003 PMC Full Text View journal details
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