Source:http://linkedlifedata.com/resource/pubmed/id/12021267
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
30
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| pubmed:dateCreated |
2002-7-22
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| pubmed:abstractText |
Fibulin-5 (FBLN-5; also known as DANCE or EVEC) is an integrin-binding extracellular matrix protein that mediates endothelial cell adhesion; it is also a calcium-dependent elastin-binding protein that scaffolds cells to elastic fibers, thereby preventing elastinopathy in the skin, lung, and vasculature. Transforming growth factor-beta (TGF-beta) regulates the production of cytokines, growth factors, and extracellular matrix proteins by a variety of cell types and tissues. We show here that TGF-beta stimulates murine 3T3-L1 fibroblasts to synthesize FBLN-5 transcript and protein through a Smad3-independent pathway. Overexpression of FBLN-5 in 3T3-L1 cells increased DNA synthesis and enhanced basal and TGF-beta-stimulated activation of ERK1/ERK2 and p38 mitogen-activated protein kinase (MAPK). FBLN-5 overexpression also augmented the tumorigenicity of human HT1080 fibrosarcoma cells by increasing their DNA synthesis, migration toward fibronectin, and invasion through synthetic basement membranes. In stark contrast, FBLN-5 expression was down-regulated in the majority of metastatic human malignancies, particularly in cancers of the kidney, breast, ovary, and colon. Unlike its proliferative response in fibroblasts, FBLN-5 overexpression in mink lung Mv1Lu epithelial cells resulted in an antiproliferative response, reducing their DNA synthesis and cyclin A expression. Moreover, FBLN-5 synergizes with TGF-beta in stimulating AP-1 activity in Mv1Lu cells, an effect that was abrogated by overexpression of dominant-negative versions of either MKK1 or p38 MAPKalpha. Accordingly, both the stimulation and duration of ERK1/ERK2 and p38 MAPK by TGF-beta was enhanced in Mv1Lu cells expressing FBLN-5. Our findings identify FBLN-5 as a novel TGF-beta-inducible target gene that regulates cell growth and motility in a context-specific manner and affects protein kinase activation by TGF-beta. Our findings also indicate that aberrant FBLN-5 expression likely contributes to tumor development in humans.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FBLN5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fbln5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
26
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| pubmed:volume |
277
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
27367-77
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:12021267-3T3 Cells,
pubmed-meshheading:12021267-Animals,
pubmed-meshheading:12021267-Blotting, Northern,
pubmed-meshheading:12021267-Cell Division,
pubmed-meshheading:12021267-Cell Line,
pubmed-meshheading:12021267-Cell Movement,
pubmed-meshheading:12021267-Cells, Cultured,
pubmed-meshheading:12021267-Dose-Response Relationship, Drug,
pubmed-meshheading:12021267-Epithelial Cells,
pubmed-meshheading:12021267-Extracellular Matrix Proteins,
pubmed-meshheading:12021267-Fibrosarcoma,
pubmed-meshheading:12021267-Genes, Reporter,
pubmed-meshheading:12021267-Humans,
pubmed-meshheading:12021267-Luciferases,
pubmed-meshheading:12021267-Lung,
pubmed-meshheading:12021267-MAP Kinase Signaling System,
pubmed-meshheading:12021267-Mass Spectrometry,
pubmed-meshheading:12021267-Mice,
pubmed-meshheading:12021267-Mink,
pubmed-meshheading:12021267-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12021267-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12021267-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12021267-Neoplasm Invasiveness,
pubmed-meshheading:12021267-Plasmids,
pubmed-meshheading:12021267-Recombinant Proteins,
pubmed-meshheading:12021267-Retroviridae,
pubmed-meshheading:12021267-Thymidine,
pubmed-meshheading:12021267-Time Factors,
pubmed-meshheading:12021267-Tissue Distribution,
pubmed-meshheading:12021267-Transforming Growth Factor beta,
pubmed-meshheading:12021267-Tumor Cells, Cultured
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| pubmed:year |
2002
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| pubmed:articleTitle |
Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades.
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| pubmed:affiliation |
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. schiemannwp@njc.org
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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