論文 - 詳細
| RRC ID | 43348 |
|---|---|
| 著者 | Maehata T, Taniguchi H, Yamamoto H, Nosho K, Adachi Y, Miyamoto N, Miyamoto C, Akutsu N, Yamaoka S, Itoh F. |
| タイトル | Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer. |
| ジャーナル | World J Gastroenterol |
| Abstract |
AIM:To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer. METHODS:We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR (MSP). Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS:Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro. CONCLUSION:Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis. |
| 巻・号 | 14(17) |
| ページ | 2702-14 |
| 公開日 | 2008-5-7 |
| DOI | 10.3748/wjg.14.2702 |
| PMID | 18461655 |
| PMC | PMC2709050 |
| MeSH | Adaptor Proteins, Signal Transducing Cell Line, Tumor Cell Proliferation Chemokines CpG Islands* DNA Methylation* Gastrointestinal Neoplasms / genetics* Gastrointestinal Neoplasms / metabolism Gastrointestinal Neoplasms / pathology Gene Expression Regulation, Neoplastic* Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins / genetics* Intercellular Signaling Peptides and Proteins / metabolism Membrane Proteins / genetics Neoplasm Invasiveness Promoter Regions, Genetic RNA Interference* RNA, Messenger / metabolism RNA, Small Interfering / metabolism Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics Tissue Array Analysis Transcription, Genetic* Transfection beta Catenin / genetics |
| IF | 3.665 |
| 引用数 | 53 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | TGBC2TKB(RCB1130) TGBC1TKB(RCB1129) |