Source:http://linkedlifedata.com/resource/pubmed/id/16489046
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2006-2-20
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pubmed:abstractText |
Insulin-like growth factor-I (IGF-I), IGF-II, and insulin have all been implicated in regulating several aspects of the malignant phenotype via the type I IGF receptor (IGF1R) and insulin receptor (IR). We have previously shown that a chimeric single-chain antibody against IGF1R (scFv-Fc) and a murine antibody EM164 down-regulate IGF1R, making breast cancer cells unresponsive to IGF-I. To determine if IR signaling is affected, we examined regulation of IR in MCF-7 cells after exposure to these antibodies. Surprisingly, both scFv-Fc and EM164 resulted in decreased levels of IR in vitro and in vivo despite their lack of reactivity against IR. Twenty-four-hour pretreatment with EM164 also inhibited insulin-mediated phosphorylation of IR and insulin-stimulated proliferation of MCF-7 cells. Neither scFv-Fc nor EM164 caused down-regulation of IR in cells that express very low levels of IGF1R or no IGF1R. Expression of IGF1R was required for IR down-regulation, which was specific as neither antibody caused down-regulation of beta1 integrin or epidermal growth factor receptor. Reagents that disrupt lipid rafts inhibited IR down-regulation by the antibodies, suggesting that IR in close physical proximity to IGF1R in lipid rafts was being endocytosed. Our data show that down-regulation of IR by monoclonal antibodies against IGF1R requires the coexpression of IGF1R and may be due to endocytosis of hybrid IR/IGF1R or holo-IR. Thus, antibodies against IGF1R provide inhibition of both IGF and insulin signaling in cancer cells.
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pubmed:grant | |
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 |
Feb
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
66
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2391-402
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16489046-Animals,
pubmed-meshheading:16489046-Antibodies,
pubmed-meshheading:16489046-Antibody Specificity,
pubmed-meshheading:16489046-Breast Neoplasms,
pubmed-meshheading:16489046-Cell Line, Tumor,
pubmed-meshheading:16489046-Down-Regulation,
pubmed-meshheading:16489046-Female,
pubmed-meshheading:16489046-Humans,
pubmed-meshheading:16489046-Immunoglobulin Fragments,
pubmed-meshheading:16489046-Membrane Microdomains,
pubmed-meshheading:16489046-Mice,
pubmed-meshheading:16489046-Receptor, IGF Type 1,
pubmed-meshheading:16489046-Receptor, Insulin,
pubmed-meshheading:16489046-Xenograft Model Antitumor Assays
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pubmed:year |
2006
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pubmed:articleTitle |
Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer.
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pubmed:affiliation |
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA. sachd003@umn.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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