Loss-of-function mutations in the transcription factor 7 (T cell factor-1) gene in hepatogastrointestinal cancers
DC Field | Value | Language |
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dc.contributor.author | Jung, Kwang Hwa | - |
dc.contributor.author | Yoon, Kang Jun | - |
dc.contributor.author | Song, Jae Hwi | - |
dc.contributor.author | Lee, Sung Hak | - |
dc.contributor.author | Eun, Jung Woo | - |
dc.contributor.author | Noh, Ji Heon | - |
dc.contributor.author | Kim, Jeong Kyu | - |
dc.contributor.author | Bae, Hyun Jin | - |
dc.contributor.author | Lee, Jang Eun | - |
dc.contributor.author | Kim, Sang Woo | - |
dc.contributor.author | Choi, Myung Gyu | - |
dc.contributor.author | Kim, Su Young | - |
dc.contributor.author | Park, Won Sang | - |
dc.contributor.author | Nam, Suk Woo | - |
dc.contributor.author | Lee, Jung Young | - |
dc.date.accessioned | 2023-03-08T23:01:42Z | - |
dc.date.available | 2023-03-08T23:01:42Z | - |
dc.date.issued | 2010-09 | - |
dc.identifier.issn | 1738-642X | - |
dc.identifier.issn | 2092-8467 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/65073 | - |
dc.description.abstract | Inappropriate activation of the Wnt signaling pathway has been repeatedly implicated in the tumorigenesis of colon, liver, and gastric cancers. There is accumulating evidences that transcriptional factor 7 (TCF7; also called T cell factor 1) might also be one of the tumor suppressor genes in the Wnt pathway. We performed PCR-based sequencing analysis of the TCF7 gene in 234 alimentary tract cancers. The TCF7 mutants detected in this study were functionally analyzed after they were generated by a QuickChange site-directed mutagenesis kit. We detected 7 somatic mutations in the TCF7 gene, including 4 missense, 2 frameshift, and one 28-bp deletion. In a yeast twohybrid assay, most of the mutants showed varying degrees of decreased binding to an amino-terminal enhancer of split (AES), a truncated form of Grouchorelated protein lacking WD40 repeats. To determine whether mutant TCF7 proteins had decreased DNA binding, we performed electrophoretic mobility shift assays, and the 2 frameshift mutants were shown to have no DNA binding activity. Furthermore, luciferase reporter assays revealed that TCF7 mutants in the presence of AES failed in the AES-dependent transcriptional repression of the reporter gene. In addition, human embryonic kidney 293 cells transfected with TCF7 mutants expressed high levels of cyclin D1, up to 6 times more than cells transfected with wild-type TCF7. Therefore, the TCF7 mutations detected in this study seem to be loss-of-function mutations caused by loss of TCF7 repressor activity through decreased binding to Groucho-related protein and/or DNA, thereby contributing to neoplastic transformation by causing accumulation of cylin D1. | - |
dc.format.extent | 8 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.title | Loss-of-function mutations in the transcription factor 7 (T cell factor-1) gene in hepatogastrointestinal cancers | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s13273-010-0037-y | - |
dc.identifier.bibliographicCitation | Molecular and Cellular Toxicology, v.6, no.3, pp 271 - 278 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-79951895134 | - |
dc.citation.endPage | 278 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 271 | - |
dc.citation.title | Molecular and Cellular Toxicology | - |
dc.citation.volume | 6 | - |
dc.type.docType | Article | - |
dc.publisher.location | 대한민국 | - |
dc.subject.keywordAuthor | Alimentary tract cancers | - |
dc.subject.keywordAuthor | Loss of heterozygosity | - |
dc.subject.keywordAuthor | Somatic mutations | - |
dc.subject.keywordAuthor | TCF7 | - |
dc.subject.keywordAuthor | Wnt signaling pathway | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kciCandi | - |
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