Somatic mutation and SNP in the promoter of dbpA and human hepatocarcinogenesis
| Autor: | Yasuyuki Arakawa, Seigo Takano, Okio Hino, Masatoshi Kudo, Tomoyuki Umeda, Junpei Hayashi, Kazunori Kajino |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Transcription Genetic Blotting Western Molecular Sequence Data Biology Transfection DNA-binding protein Polymorphism Single Nucleotide Germline mutation Transcription (biology) Tumor Cells Cultured Humans Transversion Luciferases Promoter Regions Genetic Gene Heat-Shock Proteins Genetics Binding Sites Base Sequence Binding protein Liver Neoplasms Promoter Cold-shock domain Molecular biology DNA-Binding Proteins Blotting Southern Oncology Mutation CCAAT-Enhancer-Binding Proteins Carrier Proteins |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1019-6439 |
| Popis: | Human DNA-binding protein (dbpA) is a member of a Y-box binding protein family containing a cold shock domain. The increased expression of Y box binding proteins in somatic cells is associated with cell proliferation and transformation. Recently, we isolated a splicing variant of dbpA as a candidate for the cellular recombinogenic protein that leads to genomic instability and inflammation-mediated hepatocarcinogenesis. The expression of dbpA is enhanced in proliferating cells, but the manner in which it regulates transcription is largely unknown. In this study, we analyzed the transcriptional regulatory region of dbpA, and searched for the mutation in this region by a direct sequence method. In 3 of 55 human hepatocellular carcinoma (HCC) cases, we identified one nucleotide replacement (T right curved arrow G transversion) in nucleotide position -6 of the promoter region. Among 3 cases showing this transversion, one HCC case was due to a somatic mutation and the other two were due to single nucleotide polymorphism (SNP). By luciferase assay, we showed that the transcriptional activity of the promoter region with the transversion was significantly higher than that of the wild-type. Using the Southwestern blotting, we also confirmed the existence of a cellular proteins (about 25 and 50 kDa) that specifically bind to the sequence with this transversion. Our results suggested the biological significance of the transversion of dbpA's promoter region as one of the factors accelerating hepatocarcinogenesis. |
| Databáze: | OpenAIRE |
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