Source:http://linkedlifedata.com/resource/pubmed/id/18818673
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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0022567,
umls-concept:C0078058,
umls-concept:C0206745,
umls-concept:C0871261,
umls-concept:C1256770,
umls-concept:C1510438,
umls-concept:C1519346,
umls-concept:C1527178,
umls-concept:C1704632,
umls-concept:C1705938,
umls-concept:C1706817,
umls-concept:C2348480,
umls-concept:C2911692
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pubmed:issue |
3
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pubmed:dateCreated |
2009-2-11
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pubmed:abstractText |
Vascular endothelial growth factor (VEGF-A) is a critical player in cutaneous angiogenesis. However, the relative contribution of VEGF-A from different sources including epithelial and mesenchymal cells has not been fully characterized during skin repair and tumorigenesis. Moreover, the actual involvement of other vascular-specific acting molecules has remained elusive in part due to the masking and/or overlapping effects of VEGF-A. To shed light on these uncertainties we generated and characterized a clonal VEGF-null mouse keratinocyte cell line, through in vitro adenoviral gene transfer of Cre recombinase to VEGF-LoxP primary keratinocytes followed by repeated cell passaging under controlled conditions and cloning. In vitro and in vivo assays demonstrated that VEGF-null keratinocytes were nontumorigenic and expressed normal differentiation markers after calcium switch. Hras-induced tumorigenesis of immortalized VEGF-null keratinocytes upon subcutaneous injection was markedly reduced but not fully suppressed. However, the metastatic ability of Hras-transformed VEGF-null keratinocytes was abolished. These ex vivo approaches suggest the existence of VEGF-dependent and independent angiogenic stimuli in skin carcinogenesis. The VEGF-null mouse keratinocyte cell line arises as an important tool to assess the actual contribution of keratinocyte-derived VEGF with respect to other angiogenic factors in skin homeostasis and malignancy.
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pubmed:commentsCorrections | |
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 |
Mar
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pubmed:issn |
1523-1747
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
129
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
730-41
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pubmed:meshHeading |
pubmed-meshheading:18818673-Adenoviridae,
pubmed-meshheading:18818673-Alleles,
pubmed-meshheading:18818673-Animals,
pubmed-meshheading:18818673-Calcium,
pubmed-meshheading:18818673-Cell Differentiation,
pubmed-meshheading:18818673-Cell Line,
pubmed-meshheading:18818673-Gene Transfer Techniques,
pubmed-meshheading:18818673-Keratinocytes,
pubmed-meshheading:18818673-Mice,
pubmed-meshheading:18818673-Neoplasm Metastasis,
pubmed-meshheading:18818673-Neovascularization, Pathologic,
pubmed-meshheading:18818673-Skin,
pubmed-meshheading:18818673-Skin Neoplasms,
pubmed-meshheading:18818673-Vascular Endothelial Growth Factor A,
pubmed-meshheading:18818673-ras Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
Complexity of VEGF responses in skin carcinogenesis revealed through ex vivo assays based on a VEGF-A null mouse keratinocyte cell line.
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pubmed:affiliation |
Cutaneous Disease Modelling Unit, Epithelial Biomedicine Division, Basic Research Department, CIEMAT-CIBERER, Madrid, Spain.
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pubmed:publicationType |
Journal Article
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