rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-7-24
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pubmed:abstractText |
AT/RTs (atypical teratoid/rhabdoid tumours) of the CNS (central nervous system) are childhood malignancies associated with poor survival rates due to resistance to conventional treatments such as chemotherapy. We characterized a panel of human AT/RT and MRT (malignant rhabdoid tumour) cell lines for expression of RTKs (receptor tyrosine kinases) and their involvement in tumour growth and survival. When compared with normal brain tissue, AT/RT cell lines overexpressed the IR (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor). Moreover, insulin was secreted by AT/RT cells grown in serum-free medium. Insulin potently activated Akt (also called protein kinase B) in AT/RT cells, as compared with other growth factors, such as epidermal growth factor. Pharmacological inhibitors, neutralizing antibodies, or RNAi (RNA interference) targeting the IR impaired the growth of AT/RT cell lines and induced apoptosis. Inhibitors of the PI3K (phosphoinositide 3-kinase)/Akt pathway also impaired basal and insulin-stimulated AT/RT cell proliferation. Experiments using RNAi and isoform-specific pharmacological inhibitors established a key role for the class I(A) PI3K p110alpha isoform in AT/RT cell growth and insulin signalling. Taken together, our results reveal a novel role for autocrine signalling by insulin and the IR in growth and survival of malignant human CNS tumour cells via the PI3K/Akt pathway.
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pubmed:commentsCorrections |
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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/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
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/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/SMARCB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
406
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
57-66
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17506723-Autocrine Communication,
pubmed-meshheading:17506723-Brain Neoplasms,
pubmed-meshheading:17506723-Cell Line, Tumor,
pubmed-meshheading:17506723-Cell Proliferation,
pubmed-meshheading:17506723-Child, Preschool,
pubmed-meshheading:17506723-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:17506723-Culture Media, Serum-Free,
pubmed-meshheading:17506723-DNA-Binding Proteins,
pubmed-meshheading:17506723-Down-Regulation,
pubmed-meshheading:17506723-Enzyme Activation,
pubmed-meshheading:17506723-Female,
pubmed-meshheading:17506723-Growth Substances,
pubmed-meshheading:17506723-Humans,
pubmed-meshheading:17506723-Infant,
pubmed-meshheading:17506723-Insulin,
pubmed-meshheading:17506723-Isoenzymes,
pubmed-meshheading:17506723-Male,
pubmed-meshheading:17506723-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17506723-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17506723-RNA, Small Interfering,
pubmed-meshheading:17506723-Receptor, IGF Type 1,
pubmed-meshheading:17506723-Receptor, Insulin,
pubmed-meshheading:17506723-Signal Transduction,
pubmed-meshheading:17506723-Transcription Factors
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pubmed:year |
2007
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pubmed:articleTitle |
Novel role for insulin as an autocrine growth factor for malignant brain tumour cells.
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pubmed:affiliation |
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland. Alexandre.Arcaro@kispi.unizh.ch
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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