DNA methylation and histone deacetylation associated with silencing DAP kinase gene expression in colorectal and gastric cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-06-07

AUTHORS

A Satoh, M Toyota, F Itoh, T Kikuchi, T Obata, Y Sasaki, H Suzuki, A Yawata, M Kusano, M Fujita, M Hosokawa, K Yanagihara, T Tokino, K Imai

ABSTRACT

Death-associated protein kinase is a positive regulator of programmed cell death induced by interferon γ. To investigate the role of epigenetic inactivation of death-associated protein kinase in gastrointestinal cancer, we examined the methylation status of the 5′ CpG island of the death-associated protein kinase gene. Methylation of the 5′ CpG island was detected in 3 of 9 colorectal and 3 of 17 gastric cancer cell lines, while among primary tumours, it was detected in 4 of 28 (14%) colorectal and 4 of 27 (15%) gastric cancers. By contrast, methylation of the edge of the CpG island was detected in virtually every sample examined. Death-associated protein kinase expression was diminished in four cell lines that showed dense methylation of the 5′ CpG island, and treatment with 5-aza-2′-deoxycitidine, a methyltransferase inhibitor, restored gene expression. Acetylation of histones H3 and H4 in the 5′ region of the gene was assessed by chromatin immunoprecipitation and was found to correlate directly with gene expression and inversely with DNA methylation. Thus, aberrant DNA methylation and histone deacetylation of the 5′ CpG island, but not the edge of the CpG island, appears to play a key role in silencing death-associated protein kinase expression in gastrointestinal malignancies. More... »

PAGES

1817-1823

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6600319

DOI

http://dx.doi.org/10.1038/sj.bjc.6600319

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050650257

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12087472


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29 schema:description Death-associated protein kinase is a positive regulator of programmed cell death induced by interferon γ. To investigate the role of epigenetic inactivation of death-associated protein kinase in gastrointestinal cancer, we examined the methylation status of the 5′ CpG island of the death-associated protein kinase gene. Methylation of the 5′ CpG island was detected in 3 of 9 colorectal and 3 of 17 gastric cancer cell lines, while among primary tumours, it was detected in 4 of 28 (14%) colorectal and 4 of 27 (15%) gastric cancers. By contrast, methylation of the edge of the CpG island was detected in virtually every sample examined. Death-associated protein kinase expression was diminished in four cell lines that showed dense methylation of the 5′ CpG island, and treatment with 5-aza-2′-deoxycitidine, a methyltransferase inhibitor, restored gene expression. Acetylation of histones H3 and H4 in the 5′ region of the gene was assessed by chromatin immunoprecipitation and was found to correlate directly with gene expression and inversely with DNA methylation. Thus, aberrant DNA methylation and histone deacetylation of the 5′ CpG island, but not the edge of the CpG island, appears to play a key role in silencing death-associated protein kinase expression in gastrointestinal malignancies.
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36 DAP kinase gene expression
37 DNA methylation
38 H3
39 H4
40 aberrant DNA methylation
41 acetylation
42 cancer
43 cancer cell lines
44 cell death
45 cell lines
46 chromatin immunoprecipitation
47 colorectal
48 contrast
49 deacetylation
50 death
51 death-associated protein kinase
52 death-associated protein kinase expression
53 death-associated protein kinase gene
54 dense methylation
55 edge
56 epigenetic inactivation
57 expression
58 gastric cancer
59 gastric cancer cell lines
60 gastrointestinal cancer
61 gastrointestinal malignancies
62 gene expression
63 genes
64 histone H3
65 histone deacetylation
66 immunoprecipitation
67 inactivation
68 inhibitors
69 interferon γ
70 islands
71 key role
72 kinase
73 kinase expression
74 kinase gene
75 kinase gene expression
76 lines
77 malignancy
78 methylation
79 methylation status
80 methyltransferase inhibitor
81 positive regulator
82 primary tumor
83 protein kinase
84 protein kinase expression
85 protein kinase gene
86 region
87 regulator
88 role
89 samples
90 status
91 treatment
92 tumors
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