Source:http://linkedlifedata.com/resource/pubmed/id/19165858
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2009-3-30
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| pubmed:abstractText |
IGF-1 receptor (IGF-1R) plays a key role in the development of numerous tumors. Blockade of IGF-1R axis using monoclonal antibodies constitutes an interesting approach to inhibit tumor growth. We have previously shown that h7C10, a humanized anti-IGF-1R Mab, exhibited potent antitumor activity in vivo. However, mechanisms of action of h7C10 are still unknown. Here, we showed that h7C10 inhibited IGF-1-induced IGF-1R phosphorylation in a dose-dependent manner. Also, h7C10 abolished IGF-1-induced activation of PI3K/AKT and MAPK pathways. Cell cycle progression and colony formation were affected in the presence of h7C10 probably because of the inhibition of IGF-1-induced cyclin D1 and E expression. In addition, we demonstrated that h7C10 induced a rapid IGF-1R internalization leading to an accumulation into cytoplasm resulting in receptor degradation. Using lysosome and proteasome inhibitors, we observed that the IGF-1R alpha- and beta-chains could follow different degradation routes. Thus, we demonstrated that antitumoral properties of h7C10 are the result of IGF-1-induced cell signaling inhibition and down-regulation of IGF-1R level suggesting that h7C10 could be a candidate for therapeutic applications.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1097-0215
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| pubmed:author | |
| pubmed:copyrightInfo |
(c) 2008 Wiley-Liss, Inc.
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| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
124
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2281-93
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:19165858-Animals,
pubmed-meshheading:19165858-Antibodies, Monoclonal,
pubmed-meshheading:19165858-Base Sequence,
pubmed-meshheading:19165858-Cyclins,
pubmed-meshheading:19165858-Female,
pubmed-meshheading:19165858-Flow Cytometry,
pubmed-meshheading:19165858-Humans,
pubmed-meshheading:19165858-Immunoprecipitation,
pubmed-meshheading:19165858-Lysosomes,
pubmed-meshheading:19165858-MAP Kinase Signaling System,
pubmed-meshheading:19165858-Mice,
pubmed-meshheading:19165858-Microscopy, Fluorescence,
pubmed-meshheading:19165858-Phosphorylation,
pubmed-meshheading:19165858-RNA, Small Interfering,
pubmed-meshheading:19165858-Receptor, IGF Type 1,
pubmed-meshheading:19165858-Retinoblastoma Protein,
pubmed-meshheading:19165858-Transplantation, Heterologous,
pubmed-meshheading:19165858-Ubiquitination
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| pubmed:year |
2009
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| pubmed:articleTitle |
Molecular mechanisms involved in activity of h7C10, a humanized monoclonal antibody, to IGF-1 receptor.
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| pubmed:affiliation |
Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, BP 60497, Saint-Julien-en-Genevois, France. matthieu.broussas@pierre-fabre.com
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| pubmed:publicationType |
Journal Article
|