Aberrant Methylation and Histone Deacetylation Associated with Silencing of SLC5A8 in Gastric Cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-09-02

AUTHORS

Masako Ueno, Minoru Toyota, Kimishige Akino, Hiromu Suzuki, Masanobu Kusano, Ayumi Satoh, Hiroaki Mita, Yasushi Sasaki, Masanori Nojima, Kazuyoshi Yanagihara, Yuji Hinoda, Takashi Tokino, Kohzoh Imai

ABSTRACT

Aberrant methylation of a sodium co-transporter, solute carrier family 5 member 8 gene (SLC5A8), has been detected in a subset of colorectal cancers, suggesting SLC5A8 may also serve as a tumor suppressor. To further investigate the role of epigenetic inactivation of SLC5A8 expression in gastric cancer, we determined the methylation status of the SLC5A8 5' CpG island (CGI) in a panel of gastric cancer cell lines and primary gastric cancers. We detected methylation of the 5'CGI in ten of twelve gastric cancer cell lines, and five of those showed dense methylation, which correlated with the absence of SLC5A8 transcription. Aberrant methylation of SLC5A8 was also detected in 23 of 71 (30%) primary gastric cancers, indicating that epigenetic inactivation of SLC5A8 is not a cell-line-specific phenomenon. SLC5A8 expression was restored in methylated cell lines by treatment with 5-aza-2'-deoxycytidine, a methyltransferase inhibitor. In addition, chromatin immunoprecipitation assays showed that acetylation of histone H3 in the 5' region of the gene correlated directly with SLC5A8 expression and inversely with DNA methylation. It thus appears that aberrant methylation of its 5'CGI and histone deacetylation play key roles in silencing SLC5A8 expression in gastric cancers. More... »

PAGES

134-140

Identifiers

URI

http://scigraph.springernature.com/pub.10.1159/000079145

DOI

http://dx.doi.org/10.1159/000079145

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033370551

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15361710


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22 schema:description Aberrant methylation of a sodium co-transporter, solute carrier family 5 member 8 gene (SLC5A8), has been detected in a subset of colorectal cancers, suggesting SLC5A8 may also serve as a tumor suppressor. To further investigate the role of epigenetic inactivation of SLC5A8 expression in gastric cancer, we determined the methylation status of the SLC5A8 5' CpG island (CGI) in a panel of gastric cancer cell lines and primary gastric cancers. We detected methylation of the 5'CGI in ten of twelve gastric cancer cell lines, and five of those showed dense methylation, which correlated with the absence of SLC5A8 transcription. Aberrant methylation of SLC5A8 was also detected in 23 of 71 (30%) primary gastric cancers, indicating that epigenetic inactivation of SLC5A8 is not a cell-line-specific phenomenon. SLC5A8 expression was restored in methylated cell lines by treatment with 5-aza-2'-deoxycytidine, a methyltransferase inhibitor. In addition, chromatin immunoprecipitation assays showed that acetylation of histone H3 in the 5' region of the gene correlated directly with SLC5A8 expression and inversely with DNA methylation. It thus appears that aberrant methylation of its 5'CGI and histone deacetylation play key roles in silencing SLC5A8 expression in gastric cancers.
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28 schema:keywords Associated
29 CpG islands
30 DNA methylation
31 H3
32 SLC5A8
33 SLC5A8 expression
34 aberrant methylation
35 absence
36 acetylation
37 addition
38 assays
39 cancer
40 cancer cell lines
41 cell lines
42 chromatin immunoprecipitation assays
43 colorectal cancer
44 deacetylation
45 dense methylation
46 epigenetic inactivation
47 expression
48 gastric cancer
49 gastric cancer cell lines
50 genes
51 histone H3
52 histone deacetylation
53 immunoprecipitation assays
54 inactivation
55 inhibitors
56 islands
57 key role
58 lines
59 methylated cell lines
60 methylation
61 methylation status
62 methyltransferase inhibitor
63 panel
64 phenomenon
65 primary gastric cancer
66 region
67 role
68 silencing
69 sodium
70 specific phenomena
71 status
72 subset
73 suppressor
74 transcription
75 treatment
76 tumor suppressor
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