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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
DC Field | Value | Language |
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dc.contributor.author | Kim, Seung-Kyoon | - |
dc.contributor.author | Jang, Hay-Ran | - |
dc.contributor.author | Kim, Jeong-Hwan | - |
dc.contributor.author | Kim, Mirang | - |
dc.contributor.author | Noh, Seung-Moo | - |
dc.contributor.author | Song, Kyu-Sang | - |
dc.contributor.author | Kang, Gyeong Hoon | - |
dc.contributor.author | Kim, Hee Jin | - |
dc.contributor.author | Kim, Seon-Young | - |
dc.contributor.author | Yoo, Hyang-Sook | - |
dc.contributor.author | Kim, Yong Sung | - |
dc.date.accessioned | 2009-06-04T06:45:56Z | - |
dc.date.available | 2009-06-04T06:45:56Z | - |
dc.date.issued | 2008-07-16 | - |
dc.identifier.citation | Carcinogenesis, 29, 1623-1631 | en |
dc.identifier.issn | 0143-3334 (print) | - |
dc.identifier.issn | 1460-2180 (online) | - |
dc.identifier.uri | https://hdl.handle.net/10371/4420 | - |
dc.description.abstract | Transcriptional 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. | en |
dc.description.sponsorship | 21C Frontier Functional Human Genome Project (FG08-11-01) from the Ministry of Science and Technology of Korea. | en |
dc.language.iso | en | - |
dc.publisher | Oxford University Press | en |
dc.title | 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 | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 김승균 | - |
dc.contributor.AlternativeAuthor | 장해란 | - |
dc.contributor.AlternativeAuthor | 김정환 | - |
dc.contributor.AlternativeAuthor | 김미랑 | - |
dc.contributor.AlternativeAuthor | 노승무 | - |
dc.contributor.AlternativeAuthor | 송규상 | - |
dc.contributor.AlternativeAuthor | 강경훈 | - |
dc.contributor.AlternativeAuthor | 김희진 | - |
dc.contributor.AlternativeAuthor | 김선영 | - |
dc.contributor.AlternativeAuthor | 유향숙 | - |
dc.contributor.AlternativeAuthor | 김용성 | - |
dc.identifier.doi | 10.1093/carcin/bgn110 | - |
dc.identifier.doi | 10.1093/carcin/bgn110 | - |
dc.citation.journaltitle | Carcinogenesis | - |
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