Source:http://linkedlifedata.com/resource/pubmed/id/17890288
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2008-2-1
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| pubmed:abstractText |
beta-arrestins (beta-Arrs) are known to be associated with tumor signaling pathways such as transforming growth factor-beta1 (TGF-beta1), P53/Murine double minute (MDM2) and NF-kappaB. To investigate the role of beta-Arr in tumor progression in vivo, we generated beta-Arr transgenic mice by subcutaneously inoculating tumor cells in them. We found that the xenograft tumor initiated earlier and grew more rapidly in beta-Arr1 transgenic mice than in both the beta-Arr2 transgenic and wild-type mice after inoculating murine liver cancer Hepa1-6 cells or lymphoma EL4 cells. Moreover, matrix metalloproteinase 9 (MMP9) activity, vascular endothelial growth factor (VEGF) concentration in plasma and new small blood vessel formation in tumor tissues were enhanced in beta-Arr1 transgenic mice compared with those in control mice. In addition, injection of MMP9 inhibitors in beta-Arr1 transgenic mice abrogated all these effects and suppressed rapid tumor progression. Similar results were observed in human microvascular endothelial cells, where overexpressed beta-Arr1 did increase MMP9 activity and small blood vessel formation. Furthermore, phosphatidylinositol 3-kinase (PI3K) inhibitors could suppress beta-Arr1-enhanced MMP9 activity and the C-terminal 181-418 amino acids (aa) of beta-Arr1 was largely responsible for this effect. Our data reveal a functional role for beta-arrestin1 in tumor progression in vivo, in which overexpression of beta-Arr1 promotes MMP9 activity and tumor angiogenesis by providing a suitable microenvironment for tumor progression.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arrestins,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
|
| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
22
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
355-64
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:17890288-Animals,
pubmed-meshheading:17890288-Arrestins,
pubmed-meshheading:17890288-Cell Line,
pubmed-meshheading:17890288-Disease Progression,
pubmed-meshheading:17890288-Enzyme Activation,
pubmed-meshheading:17890288-Humans,
pubmed-meshheading:17890288-Matrix Metalloproteinase 9,
pubmed-meshheading:17890288-Mice,
pubmed-meshheading:17890288-Mice, Inbred C57BL,
pubmed-meshheading:17890288-Mice, Transgenic,
pubmed-meshheading:17890288-Neoplasm Transplantation,
pubmed-meshheading:17890288-Neoplasms,
pubmed-meshheading:17890288-Neovascularization, Pathologic,
pubmed-meshheading:17890288-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17890288-Signal Transduction,
pubmed-meshheading:17890288-Time Factors,
pubmed-meshheading:17890288-Transplantation, Heterologous,
pubmed-meshheading:17890288-Vascular Endothelial Growth Factor A
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| pubmed:year |
2008
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| pubmed:articleTitle |
Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis.
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| pubmed:affiliation |
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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