Source:http://linkedlifedata.com/resource/pubmed/id/17581609
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2007-8-22
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| pubmed:abstractText |
Insulin-like growth factor (IGF) signaling plays an important role in various human cancers. Therefore, the role of insulin-like growth factor I (IGF-I) signaling in growth and survival of acute myeloid leukemia (AML) cells was investigated. Expression of the IGF-I receptor (IGF-IR) and its ligand IGF-I were detected in a panel of human AML blasts and cell lines. IGF-I and insulin promoted the growth of human AML blasts in vitro and activated the phosphoinositide 3-kinase (PI3K)/Akt and the extracellular signal-regulated kinase (Erk) pathways. IGF-I-stimulated growth of AML blasts was blocked by an inhibitor of the PI3K/Akt pathway. Moreover, downregulation of the class Ia PI3K isoforms p110beta and p110delta by RNA interference impaired IGF-I-stimulated Akt activation, cell growth and survival in AML cells. Proliferation of a panel of AML cell lines and blasts isolated from patients with AML was inhibited by the IGF-IR kinase inhibitor NVP-AEW541 or by an IGF-IR neutralizing antibody. In addition to its antiproliferative effects, NVP-AEW541 sensitized primary AML blasts and cell lines to etoposide-induced apoptosis. Together, our data describe a novel role for autocrine IGF-I signaling in the growth and survival of primary AML cells. IGF-IR inhibitors in combination with chemotherapeutic agents may represent a novel approach to target human AML.
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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,
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0887-6924
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
21
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1921-30
|
| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:17581609-Acute Disease,
pubmed-meshheading:17581609-Antibodies,
pubmed-meshheading:17581609-Antimetabolites, Antineoplastic,
pubmed-meshheading:17581609-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17581609-Apoptosis,
pubmed-meshheading:17581609-Autocrine Communication,
pubmed-meshheading:17581609-Cell Division,
pubmed-meshheading:17581609-Cell Line, Tumor,
pubmed-meshheading:17581609-Cytarabine,
pubmed-meshheading:17581609-Down-Regulation,
pubmed-meshheading:17581609-Etoposide,
pubmed-meshheading:17581609-Humans,
pubmed-meshheading:17581609-Insulin-Like Growth Factor I,
pubmed-meshheading:17581609-Leukemia, Myeloid,
pubmed-meshheading:17581609-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17581609-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17581609-Receptor, IGF Type 1,
pubmed-meshheading:17581609-Signal Transduction
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| pubmed:year |
2007
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| pubmed:articleTitle |
Autocrine insulin-like growth factor-I signaling promotes growth and survival of human acute myeloid leukemia cells via the phosphoinositide 3-kinase/Akt pathway.
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| pubmed:affiliation |
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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