論文 - 詳細
| RRC ID | 43335 |
|---|---|
| 著者 | Torisu Y, Watanabe A, Nonaka A, Midorikawa Y, Makuuchi M, Shimamura T, Sugimura H, Niida A, Akiyama T, Iwanari H, Kodama T, Zeniya M, Aburatani H. |
| タイトル | Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by beta-catenin/TCF. |
| ジャーナル | Cancer Sci |
| Abstract |
The Drosophila Notum gene, which is regulated by the Wingless pathway, encodes a secreted hydrolase that modifies heparan sulfate proteoglycans. In comparative analysis of the gene expression profiles in primary human hepatocellular carcinomas (HCC) and normal organs, we observed that the human ortholog of Drosophila Notum was overexpressed markedly in a subset of HCC, but expressed rarely in adult normal tissues. Immunoblotting confirmed the overexpression of NOTUM protein in 12 of 40 primary HCC cases (30%). High levels of NOTUM protein were significantly associated with intracellular (nuclear or cytoplasmic) accumulation of beta-catenin protein: all 10 HCC with high intracellular beta-catenin also had high NOTUM expression, whereas only 2 of 30 cases (6.7%) without intracellular beta-catenin had high NOTUM expression (P < 0.00001). NOTUM expression in HepG2 cells was downregulated significantly by induction of a dominant-negative mutant of TCF4, a beta-catenin partner. In vivo binding of the beta-catenin/TCF complex to the NOTUM promoter was demonstrated by chromatin immunoprecipitation in HepG2 and SW480 cells, where canonical Wnt signaling is activated constitutively. These findings provide evidence that NOTUM is a novel target of beta-catenin/TCF4 and is upregulated in Wnt/beta-catenin signaling-activated HCC. |
| 巻・号 | 99(6) |
| ページ | 1139-46 |
| 公開日 | 2008-6-1 |
| DOI | 10.1111/j.1349-7006.2008.00814.x |
| PII | CAS814 |
| PMID | 18429952 |
| MeSH | Adult Aged Animals Antibodies, Monoclonal Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology Chromatin Immunoprecipitation Drosophila Proteins / genetics* Drosophila Proteins / immunology Drosophila Proteins / metabolism Female Gene Expression Profiling Gene Expression Regulation, Neoplastic* Humans Immunization Immunoblotting Liver Neoplasms / genetics* Liver Neoplasms / metabolism Liver Neoplasms / pathology Male Mice Middle Aged Mutagenesis, Site-Directed Oligonucleotide Array Sequence Analysis Promoter Regions, Genetic Rabbits Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / immunology Recombinant Fusion Proteins / metabolism Signal Transduction TCF Transcription Factors / genetics TCF Transcription Factors / metabolism Transcription Factor 7-Like 2 Protein Transcription, Genetic* Tumor Cells, Cultured beta Catenin / metabolism* |
| IF | 4.966 |
| 引用数 | 34 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN1(RCB1003) HeLa(RCB0007) |