| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MKN1(RCB1003)
HeLa(RCB0007) |
