CpG methylation in exon 1 of transcription factor 4 increases with age in normal gastric mucosa and is associated with gene silencing in intestinal-type gastric cancers

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dc.contributor.authorSeung Kyoon Kim-
dc.contributor.authorHay Ran Jang-
dc.contributor.authorJeong Hwan Kim-
dc.contributor.authorMirang Kim-
dc.contributor.authorS M Noh-
dc.contributor.authorK S Song-
dc.contributor.authorG H Kang-
dc.contributor.authorH J Kim-
dc.contributor.authorSeon-Young Kim-
dc.contributor.authorHyang Sook Yoo-
dc.contributor.authorYong Sung Kim-
dc.date.accessioned2017-04-19T09:11:23Z-
dc.date.available2017-04-19T09:11:23Z-
dc.date.issued2008-
dc.identifier.issn0143-3334-
dc.identifier.uri10.1093/carcin/bgn110ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/8537-
dc.description.abstractTranscriptional factor 4 (TCF4), encoding a basic helix-loop-helix transcriptional factor, has recently been demonstrated as a causative gene for Pitt-Hopkins syndrome, a neurodevelopmental disease. Examination of gastric cancers using the restriction landmark genomic scanning technique revealed methylation at a NotI enzyme site in TCF4 intron 8 and further identified CpG dinucleotide hypermethylation in TCF4 exon 1, strongly associated with gene silencing in gastric cancer cell lines. Treatment with 5-aza-2′-deoxycytidine and/or trichostatin A restored TCF4 expression in TCF4-silenced gastric cancer cell lines. Real-time reverse transcription-polymerase chain reaction analysis of 77 paired primary gastric tumor samples revealed that 38% of analyzed tumors had a >2-fold decrease in TCF4 expression compared with adjacent normal-appearing tissue, and the decrease significantly correlated with increased CpG methylation in TCF4 exon 1. Clinicopathologic data showed that decreased TCF4 expression occurred significantly more frequently in intestinal-type (22/37, 59%) than in diffuse-type (7/37, 19%) gastric cancers (P = 0.0004) and likewise more frequently in early (12/18, 67%) than in advanced (17/59, 29%) gastric cancers (P = 0.004). CpG methylation markedly increased with patient age among normal-appearing tissues, suggesting that CpG methylation in gastric mucosa may be one of the earliest events in carcinogenesis of intestinal-type gastric cancers. Furthermore, ectopic expression of TCF4 decreased cell growth in a gastric cancer cell line, and the knock down of TCF4 using small interfering RNA increased cell migration. Based on these results, we propose that the observed frequent epigenetic-mediated TCF4 silencing plays a role in tumor formation and progression.-
dc.publisherOxford Univ Press-
dc.titleCpG methylation in exon 1 of transcription factor 4 increases with age in normal gastric mucosa and is associated with gene silencing in intestinal-type gastric cancers-
dc.title.alternativeCpG methylation in exon 1 of transcription factor 4 increases with age in normal gastric mucosa and is associated with gene silencing in intestinal-type gastric cancers-
dc.typeArticle-
dc.citation.titleCarcinogenesis-
dc.citation.number8-
dc.citation.endPage1631-
dc.citation.startPage1623-
dc.citation.volume29-
dc.contributor.affiliatedAuthorSeung Kyoon Kim-
dc.contributor.affiliatedAuthorHay Ran Jang-
dc.contributor.affiliatedAuthorJeong Hwan Kim-
dc.contributor.affiliatedAuthorMirang Kim-
dc.contributor.affiliatedAuthorSeon-Young Kim-
dc.contributor.affiliatedAuthorHyang Sook Yoo-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeName김승균-
dc.contributor.alternativeName장해란-
dc.contributor.alternativeName김정환-
dc.contributor.alternativeName김미랑-
dc.contributor.alternativeName노승무-
dc.contributor.alternativeName송규상-
dc.contributor.alternativeName강경훈-
dc.contributor.alternativeName김희진-
dc.contributor.alternativeName김선영-
dc.contributor.alternativeName유향숙-
dc.contributor.alternativeName김용성-
dc.identifier.bibliographicCitationCarcinogenesis, vol. 29, no. 8, pp. 1623-1631-
dc.identifier.doi10.1093/carcin/bgn110-
dc.description.journalClassY-
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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