Source:http://linkedlifedata.com/resource/pubmed/id/15220935
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
2004-8-17
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| pubmed:abstractText |
E-cadherin is a cell-cell adhesion molecule that plays a pivotal role in the development and maintenance of cell polarity. Disruption of E-cadherin-mediated adhesion represents a key step toward the invasive phenotype in a variety of solid tumors, including hepatocellular carcinoma (HCC). Here, we investigate whether deregulation of E-cadherin occurs along the multistep process of hepatocarcinogenesis in transgenic mouse models, including c-Myc, E2F1, c-Myc/TGF-alpha and c-Myc/E2F1 mice. Liver tumors from the transgenic mouse lines could be divided into two categories based on E-cadherin levels. Of 28, 20 (71.4%) c-Myc HCCs showed marked reduction of E-cadherin expression when compared with wild-type livers. In contrast, all of c-Myc/TGF-alpha and the majority of E2F1 and c-myc/E2F1 preneoplastic and neoplastic lesions exhibited overexpression of E-cadherin. Downregulation of E-cadherin was associated with promoter hypermethylation in seven of 20 c-Myc HCCs (35%), while no loss of heterozygosity at the E-cadherin locus was detected. Nuclear accumulation of beta-catenin did not correlate with E-cadherin downregulation. Furthermore, c-Myc HCCs with reduced E-cadherin displayed upregulation of hypoxia-inducible factor-1alpha and vascular endothelial growth factor proteins. Importantly, loss of E-cadherin was associated with increased cell proliferation and higher microvessel density in c-Myc tumors. Taken together, these data suggest that loss of E-cadherin might favor tumor progression in relatively more benign HCC from c-Myc transgenic mice by stimulating neoplastic proliferation and angiogenesis under hypoxic conditions.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0023-6837
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
84
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1137-47
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| pubmed:meshHeading |
pubmed-meshheading:15220935-Animals,
pubmed-meshheading:15220935-Apoptosis,
pubmed-meshheading:15220935-Blotting, Western,
pubmed-meshheading:15220935-Cadherins,
pubmed-meshheading:15220935-Carcinoma, Hepatocellular,
pubmed-meshheading:15220935-DNA, Neoplasm,
pubmed-meshheading:15220935-Disease Models, Animal,
pubmed-meshheading:15220935-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15220935-Immunohistochemistry,
pubmed-meshheading:15220935-Liver Neoplasms,
pubmed-meshheading:15220935-Mice,
pubmed-meshheading:15220935-Mice, Inbred Strains,
pubmed-meshheading:15220935-Mice, Transgenic,
pubmed-meshheading:15220935-Microcirculation,
pubmed-meshheading:15220935-Microsatellite Repeats,
pubmed-meshheading:15220935-Neovascularization, Pathologic,
pubmed-meshheading:15220935-Polymerase Chain Reaction
|
| pubmed:year |
2004
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| pubmed:articleTitle |
Disregulation of E-cadherin in transgenic mouse models of liver cancer.
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| pubmed:affiliation |
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
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| pubmed:publicationType |
Journal Article
|