Downregulation of id4 by promoter hypermethylation in gastric adenocarcinoma

ABSTRACT Promoter hypermethylation has become apparent as a common mechanism of gene silencing in cancer. Based on our published microarray expression data, we noticed a prominent

downregulation of _ID4_ in gastric adenocarcinoma. The dense 5′ CpG island covering the previously mapped upstream promoter of _ID4_ has prompted us to relate its downregulation to promoter

hypermethylation. ID proteins are distinct members in the helix–loop–helix family of transcriptional regulators, which modulate various key developmental processes. Emerging data have

suggested the involvement of _ID_ genes in tumorigenesis. In this study using bisulfite genomic sequencing, we have found hypermethylation of _ID4_ promoter in most gastric cancer cell lines

and 30% of primary tumors. This correlated with decreased level of _ID4_ expression. Restoration of _ID4_ expression in various gastric cancer cell lines was achieved by treatment with the

DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine, which at times required the synergistic action of the histone deacetylase inhibitor trichostatin A, but not with trichostatin A alone.

Re-expression was accompanied by the corresponding _ID4_ promoter demethylation. Furthermore, we have found significant association of _ID4_ promoter methylation with _hMLH1_ promoter

methylation (_P_=0.008) and microsatellite instability (_P_=0.006). Overall, our results have shown that transcriptional silencing of _ID4_ is related to the aberrant methylation of its

promoter in gastric cancer. The significant association of _ID4_ and _hMLH1_ promoter hypermethylation suggested that _ID4_ may also be among the genes being targeted in the CpG island

methylator phenotype tumorigenic pathway. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access

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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS TRANSCRIPTIONAL OVERLAP LINKS DNA HYPOMETHYLATION WITH DNA HYPERMETHYLATION AT ADJACENT

PROMOTERS IN CANCER Article Open access 30 August 2021 DNMT3B OVEREXPRESSION DOWNREGULATES GENES WITH CPG ISLANDS, COMMON MOTIFS, AND TRANSCRIPTION FACTOR BINDING SITES THAT INTERACT WITH

DNMT3B Article Open access 02 December 2022 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED TUMOUR-RELATED GENES REGULATED BY UHRF1-DRIVEN DNA METHYLATION Article Open access 07 August 2024

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_Oncogene_, 20, 8317–8325. Download references ACKNOWLEDGEMENTS This work was supported by the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7006/99M and

7264/01M) and the HM Lui Foundation. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Agnes Sze Wah Chan, 

Wai Yin Tsui, Tsun Leung Chan, Annie Shuk Yee Chan, Siu Tsan Yuen & Suet Yi Leung * Department of Surgery, Stanford University School of Medicine, Stanford, 94305, CA, USA Xin Chen, Rui

Li & Samuel So * Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong Kent Man Chu Authors * Agnes Sze Wah Chan View author publications You can also search

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CORRESPONDING AUTHORS Correspondence to Siu Tsan Yuen or Suet Yi Leung. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Chan, A., Tsui, W., Chen, X. _et

al._ Downregulation of _ID4_ by promoter hypermethylation in gastric adenocarcinoma. _Oncogene_ 22, 6946–6953 (2003). https://doi.org/10.1038/sj.onc.1206799 Download citation * Received: 07

March 2003 * Revised: 20 May 2003 * Accepted: 21 May 2003 * Published: 09 October 2003 * Issue Date: 09 October 2003 * DOI: https://doi.org/10.1038/sj.onc.1206799 SHARE THIS ARTICLE Anyone

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Springer Nature SharedIt content-sharing initiative KEYWORDS * _ID4_ * _hMLH1_ * microarray * promoter methylation * gastric adenocarcinoma