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rdf:type |
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lifeskim:mentions |
umls-concept:C0003241,
umls-concept:C0018270,
umls-concept:C0044602,
umls-concept:C0109317,
umls-concept:C0140080,
umls-concept:C0243077,
umls-concept:C0285761,
umls-concept:C0752312,
umls-concept:C0752313,
umls-concept:C1150481,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1368105,
umls-concept:C1370600,
umls-concept:C1451005,
umls-concept:C1704259,
umls-concept:C1705325,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1705987,
umls-concept:C2323499
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pubmed:issue |
7
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pubmed:dateCreated |
2006-6-21
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pubmed:abstractText |
The Insulin-like growth factor-1 receptor (IGF-1R) is overexpressed in a variety of tumors including breast, prostate and myeloma. Thus, IGF-1R and its downstream signaling effectors are good candidates for molecular-based targeted antitumor therapies. Indeed, protein inhibitors of IGF-1R signaling and IGF-1R blocking antibodies are undergoing clinical trials. Herein, the molecular basis for antibody-mediated IGF-1R signal inhibition has been investigated in a hematopoietic cell line model, FDC-P1, that has been rendered interleukin-3 independent in a ligand-dependent manner through retroviral-mediated expression of IGF-1R (FD/IGF-1R). Furthermore, the ability of an anti-IGF-1R antibody to synergize with signal-transduction pathway inhibitors and induce apoptosis was determined. The alphaIGF-1R antibody, A12, was capable of arresting IGF-1 or insulin-induced FD/IGF-1R cell proliferation in the G1 phase of the cell cycle and resulted in apoptotic induction. A12 effectiveness could be potentiated through combination treatment with small molecule inhibitors of the Ras/Raf/MEK/ERK or PI3K/Akt/mTOR pathways. These results validate the use of the FD/IGF-1R cells to evaluate the effectiveness and mechanisms of targeted IGF-1R therapeutic strategies.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/raf Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0887-6924
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1254-60
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16642049-Animals,
pubmed-meshheading:16642049-Antibodies, Monoclonal,
pubmed-meshheading:16642049-Antibody Specificity,
pubmed-meshheading:16642049-Apoptosis,
pubmed-meshheading:16642049-Cell Division,
pubmed-meshheading:16642049-Cell Line, Transformed,
pubmed-meshheading:16642049-Enzyme Inhibitors,
pubmed-meshheading:16642049-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:16642049-G1 Phase,
pubmed-meshheading:16642049-Hematopoietic Stem Cells,
pubmed-meshheading:16642049-Immunotherapy,
pubmed-meshheading:16642049-Insulin-Like Growth Factor I,
pubmed-meshheading:16642049-Leukemia,
pubmed-meshheading:16642049-Mice,
pubmed-meshheading:16642049-Mitogen-Activated Protein Kinases,
pubmed-meshheading:16642049-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16642049-Protein Kinases,
pubmed-meshheading:16642049-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16642049-Receptor, IGF Type 1,
pubmed-meshheading:16642049-S Phase,
pubmed-meshheading:16642049-Signal Transduction,
pubmed-meshheading:16642049-TOR Serine-Threonine Kinases,
pubmed-meshheading:16642049-raf Kinases
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pubmed:year |
2006
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pubmed:articleTitle |
Synergy between an IGF-1R antibody and Raf/MEK/ERK and PI3K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells.
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pubmed:affiliation |
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27384, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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