Source:http://linkedlifedata.com/resource/pubmed/id/20237090
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2010-4-22
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pubmed:abstractText |
Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1). Elevated expression of vascular endothelial growth factor (VEGF) in ATL patients is associated with leukemic cell invasion and infiltration in different organs. The regulatory protein Tax 1 encoded by HTLV-1 plays a pivotal role in T-cell transformation by deregulating the function and expression of several cellular factors. In the present study, we examined the effect of Tax 1 on VEGF expression at transcriptional and posttranscriptional levels in order to elucidate the regulatory mechanisms involved. Using functional assays, we demonstrate that Tax 1 downregulates the VEGF promoter through a cluster of Sp1 sites located close to the transcriptional start site. Using gel mobility shift assays, we show that Tax 1 reduced Sp1:DNA complex formation. We demonstrate that the level of secreted VEGF was significantly lower in Tax 1-transfected 293T cells compared to nontransfected cells, which is consistent with the observed downregulatory effect of Tax 1 at the transcription level. We showed that VEGF was secreted by HTLV-1-transformed and nontransformed cells, irrespective of Tax 1 expression. Overall our data indicate that, contrary to a previous report, Tax 1 downregulates VEGF expression and suggest there are Tax 1-independent mechanisms of VEGF activation in ATL.
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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/CNTN2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, Neuronal,
http://linkedlifedata.com/resource/pubmed/chemical/Contactin 2,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1098-5514
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
84
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5222-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20237090-Cell Adhesion Molecules, Neuronal,
pubmed-meshheading:20237090-Contactin 2,
pubmed-meshheading:20237090-DNA,
pubmed-meshheading:20237090-Down-Regulation,
pubmed-meshheading:20237090-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:20237090-Human T-lymphotropic virus 1,
pubmed-meshheading:20237090-Humans,
pubmed-meshheading:20237090-Leukemia-Lymphoma, Adult T-Cell,
pubmed-meshheading:20237090-Promoter Regions, Genetic,
pubmed-meshheading:20237090-Protein Binding,
pubmed-meshheading:20237090-Up-Regulation,
pubmed-meshheading:20237090-Vascular Endothelial Growth Factor A
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pubmed:year |
2010
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pubmed:articleTitle |
Tax 1-independent induction of vascular endothelial growth factor in adult T-cell leukemia caused by human T-cell leukemia virus type 1.
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pubmed:affiliation |
Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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