Source:http://linkedlifedata.com/resource/pubmed/id/16007161
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
44
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pubmed:dateCreated |
2005-10-7
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pubmed:abstractText |
E-cadherin is a key cell adhesion molecule implicated as a tumor suppressor, which is frequently altered in hepatocellular carcinoma, especially in hepatitis B virus (HBV)-related tumors. Here, we report that HBV X protein (HBx) represses E-cadherin expression at the transcription level. Based on the differential effects of HBx natural variants, we determined that Lys-130 in the transactivation domain of HBx is critical for the E-cadherin repression. The repression effect of HBx was abolished after treatment with DNA methyltransferase inhibitor, 5'-Aza-2'dC. In addition, methylation-specific PCR analysis revealed that the CpG island 1 of E-cadherin promoter is hypermethylated by HBx. Furthermore, HBx induces DNA methyltransferase 1 expression by stimulating its transcription. Therefore, we conclude that HBx represses E-cadherin expression by inducing methylation-mediated promoter inactivation. The reduced E-cadherin expression results in dramatic morphological changes of the HBx-expressing cells. In addition, HBx-expressing cells aggregate poorly in suspension culture, reflecting their altered intercellular interactions. The biological significance was further demonstrated by the increased collagen invasion ability of HBx-expressing cells. Therefore, the present study suggests that HBx plays a role during hepatocellular carcinogenesis by favoring cell detachment from the surrounding cells and migration outside of the primary tumor site.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/DMAP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/hepatitis B virus X protein
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6617-25
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16007161-Base Sequence,
pubmed-meshheading:16007161-Cadherins,
pubmed-meshheading:16007161-Cell Line,
pubmed-meshheading:16007161-DNA Methylation,
pubmed-meshheading:16007161-DNA Primers,
pubmed-meshheading:16007161-Enzyme Activation,
pubmed-meshheading:16007161-Gene Expression Regulation,
pubmed-meshheading:16007161-Humans,
pubmed-meshheading:16007161-Promoter Regions, Genetic,
pubmed-meshheading:16007161-Repressor Proteins,
pubmed-meshheading:16007161-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16007161-Trans-Activators
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pubmed:year |
2005
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pubmed:articleTitle |
Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1.
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pubmed:affiliation |
Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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