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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0017347,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0334227,
umls-concept:C0684249,
umls-concept:C1415688,
umls-concept:C1514559,
umls-concept:C1707511,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2001-7-30
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pubmed:abstractText |
Homeobox-containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription-regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue-specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox-containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3-overexpressing A549 cells. In the HOXD3-overexpressing cell lines, expression of E-cadherin was lost and plakoglobin was strongly repressed, whereas integrin alpha3 and beta3 were up-regulated and N-cadherin and integrin alpha4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3-overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti-integrin beta1 and beta3 suggested that the increased haptotaxis of the HOXD3-overexpressing cells to vitronectin resulted from increased expression and activation of integrin alphavbeta3, and that overexpression of the HOXD3 gene converted the integrin beta1-dependent haptotaxis to fibronectin into both integrin beta1- and beta3-dependent one. HOXD3 overexpression increased production of matrix-degrative enzymes including matrix metalloproteinase-2 and urokinase-plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis-promoting gene in human lung cancer A549 cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Desmoplakins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/HOXD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha3,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin beta3,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vitronectin,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Vitronectin,
http://linkedlifedata.com/resource/pubmed/chemical/alpha Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/gamma Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0020-7136
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pubmed:author |
pubmed-author:FuruuchiKK,
pubmed-author:Hamada Ji,
pubmed-author:MiyasakiSS,
pubmed-author:MiyazakiY JYJ,
pubmed-author:MoriuchiTT,
pubmed-author:OkadaFF,
pubmed-author:OkuboYY,
pubmed-author:OmatsuTT,
pubmed-author:ShiratoHH,
pubmed-author:TadaMM,
pubmed-author:TakahashiYY,
pubmed-author:TaniguchiYY
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pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
516-25
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:11477555-Antigens, CD,
pubmed-meshheading:11477555-Cadherins,
pubmed-meshheading:11477555-Cell Movement,
pubmed-meshheading:11477555-Cytoskeletal Proteins,
pubmed-meshheading:11477555-DNA-Binding Proteins,
pubmed-meshheading:11477555-Desmoplakins,
pubmed-meshheading:11477555-Extracellular Matrix,
pubmed-meshheading:11477555-Fibronectins,
pubmed-meshheading:11477555-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11477555-Genes, Homeobox,
pubmed-meshheading:11477555-Genetic Vectors,
pubmed-meshheading:11477555-Homeodomain Proteins,
pubmed-meshheading:11477555-Humans,
pubmed-meshheading:11477555-Integrin alpha3,
pubmed-meshheading:11477555-Integrin beta3,
pubmed-meshheading:11477555-Integrins,
pubmed-meshheading:11477555-Lung Neoplasms,
pubmed-meshheading:11477555-Neoplasm Invasiveness,
pubmed-meshheading:11477555-Neoplasm Metastasis,
pubmed-meshheading:11477555-Platelet Membrane Glycoproteins,
pubmed-meshheading:11477555-Receptors, Vitronectin,
pubmed-meshheading:11477555-Trans-Activators,
pubmed-meshheading:11477555-Transfection,
pubmed-meshheading:11477555-Tumor Cells, Cultured,
pubmed-meshheading:11477555-Vitronectin,
pubmed-meshheading:11477555-alpha Catenin,
pubmed-meshheading:11477555-beta Catenin,
pubmed-meshheading:11477555-gamma Catenin
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pubmed:year |
2001
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pubmed:articleTitle |
Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells.
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pubmed:affiliation |
Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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