Source:http://linkedlifedata.com/resource/pubmed/id/19594546
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2009-9-21
|
| pubmed:abstractText |
c-Ski, originally identified as a proto-oncogene product, is an important negative regulator of transforming growth factor (TGF)-beta family signaling through interaction with Smad2, Smad3, and Smad4. High expression of c-Ski has been found in some cancers, including gastric cancer. We previously showed that disruption of TGF-beta signaling by dominant-negative TGF-beta type II receptor in a diffuse-type gastric carcinoma model accelerated tumor growth through induction of tumor angiogenesis by decreased expression of the anti-angiogenic factor thrombospondin (TSP)-1. Here, we examined the function of c-Ski in human diffuse-type gastric carcinoma OCUM-2MLN cells. Overexpression of c-Ski inhibited TGF-beta signaling in OCUM-2MLN cells. Interestingly, c-Ski overexpression resulted in extensive acceleration of the growth of subcutaneous xenografts in BALB/c nu/nu female mice (6 weeks of age). Similar to tumors expressing dominant-negative TGF-beta type II receptor, histochemical studies revealed less fibrosis and increased angiogenesis in xenografted tumors expressing c-Ski compared to control tumors. Induction of TSP-1 mRNA by TGF-beta was attenuated by c-Ski in vitro, and expression of TSP-1 mRNA was decreased in tumors expressing c-Ski in vivo. These findings suggest that c-Ski overexpression promotes the growth of diffuse-type gastric carcinoma through induction of angiogenesis.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SKI protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombospondin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
|
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
|
| pubmed:issn |
1349-7006
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
100
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1809-16
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| pubmed:meshHeading |
pubmed-meshheading:19594546-Adenocarcinoma,
pubmed-meshheading:19594546-Animals,
pubmed-meshheading:19594546-Blotting, Western,
pubmed-meshheading:19594546-Cell Line, Tumor,
pubmed-meshheading:19594546-Cell Proliferation,
pubmed-meshheading:19594546-DNA-Binding Proteins,
pubmed-meshheading:19594546-Female,
pubmed-meshheading:19594546-Humans,
pubmed-meshheading:19594546-Immunohistochemistry,
pubmed-meshheading:19594546-Mice,
pubmed-meshheading:19594546-Mice, Nude,
pubmed-meshheading:19594546-Neovascularization, Pathologic,
pubmed-meshheading:19594546-Proto-Oncogene Proteins,
pubmed-meshheading:19594546-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19594546-Signal Transduction,
pubmed-meshheading:19594546-Stomach Neoplasms,
pubmed-meshheading:19594546-Thrombospondin 1,
pubmed-meshheading:19594546-Transforming Growth Factor beta,
pubmed-meshheading:19594546-Up-Regulation,
pubmed-meshheading:19594546-Xenograft Model Antitumor Assays
|
| pubmed:year |
2009
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| pubmed:articleTitle |
c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-beta signaling in diffuse-type gastric carcinoma.
|
| pubmed:affiliation |
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|