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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-6-27
pubmed:abstractText
Wnt signaling mediated by beta-catenin plays crucial roles in the development of hepatocellular carcinoma and other cancers such as colorectal cancer. beta-Catenin associates with T-cell factor (TCF) transcription factors and functions as a transcriptional activator in the nucleus. By protein interaction screening, we identified EBP50, a cytoplasmic protein with 2 PDZ domains, as a beta-catenin-associating molecule. EBP50 interacted with beta-catenin through its carboxyl-PDZ domain in vitro and in vivo. Northern blot and RT-PCR analysis revealed an increase of EBP50 messenger RNA (mRNA) in hepatocellular carcinoma (HCC) cell lines and surgical specimens of human HCC. Over-expression of EBP50 protein with focal nuclear localization was detected in human HCC. In human HCC and colorectal cancer cell lines, EBP50 enhanced beta-catenin/TCF-dependent transcription in a dose-dependent manner. In an HCC cell line, over-expression of the carboxyl PDZ domain resulted in a decrease of endogenous beta-catenin/TCF transactivation. EBP50 promoted beta-catenin-mediated transactivation only in cells in which beta-catenin was already stabilized, suggesting that EBP50 may work with stabilized beta-catenin for transcriptional regulation. In conclusion, the EBP50/beta-catenin complex promotes Wnt signaling, and over-expression of EBP50 may work cooperatively with beta-catenin in the development of liver cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
178-86
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12830000-Carcinoma, Hepatocellular, pubmed-meshheading:12830000-Carrier Proteins, pubmed-meshheading:12830000-Cloning, Molecular, pubmed-meshheading:12830000-Cytoskeletal Proteins, pubmed-meshheading:12830000-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12830000-HeLa Cells, pubmed-meshheading:12830000-Humans, pubmed-meshheading:12830000-Liver Neoplasms, pubmed-meshheading:12830000-Phosphoproteins, pubmed-meshheading:12830000-Protein Structure, Tertiary, pubmed-meshheading:12830000-Proto-Oncogene Proteins, pubmed-meshheading:12830000-Signal Transduction, pubmed-meshheading:12830000-Sodium-Hydrogen Antiporter, pubmed-meshheading:12830000-Trans-Activators, pubmed-meshheading:12830000-Transcriptional Activation, pubmed-meshheading:12830000-Wnt Proteins, pubmed-meshheading:12830000-Zebrafish Proteins, pubmed-meshheading:12830000-beta Catenin
pubmed:year
2003
pubmed:articleTitle
EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma.
pubmed:affiliation
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't