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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0040649,
umls-concept:C0044602,
umls-concept:C0123257,
umls-concept:C0164786,
umls-concept:C0185117,
umls-concept:C0285761,
umls-concept:C0442805,
umls-concept:C0596890,
umls-concept:C0812228,
umls-concept:C0851285,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1704259,
umls-concept:C1705325,
umls-concept:C1705987,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2010-10-5
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pubmed:abstractText |
Insulin-like growth factor binding protein 2 (IGFBP-2) has been implicated in the pathophysiology of neoplasia. The PI3K/AKT/mTOR pathway has recently been shown to be a predominant regulator of IGFBP-2 at the protein level in MCF-7 breast cancer cells. However, there are gaps in knowledge with respect to the molecular mechanisms that underlie this regulation. Here, we show that the PI3K/AKT/mTOR pathway regulates IGFBP-2 protein levels by modulating IGFBP-2 mRNA abundance in MCF-7 cells. This change is achieved by regulating transcription through a critical region present in the first 200 bp upstream of the transcription initiation site where Sp1 transcription factor binds and drives transcription. IGF-1 treatment leads to increased nuclear abundance of Sp1 and increased IGFBP-2 mRNA and protein levels. Rapamycin and LY294002 induce a decline in Sp1 nuclear abundance and IGFBP-2 mRNA and protein levels. This work provides a mechanistic explanation for the observed effects of the PI3K/AKT/mTOR pathway on IGFBP-2 levels in MCF-7 cells.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Somatomedins,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1029-2292
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
243-55
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pubmed:meshHeading |
pubmed-meshheading:20370577-Blotting, Western,
pubmed-meshheading:20370577-Cell Line, Tumor,
pubmed-meshheading:20370577-Chromones,
pubmed-meshheading:20370577-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:20370577-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20370577-Fluorescent Antibody Technique,
pubmed-meshheading:20370577-Gene Expression,
pubmed-meshheading:20370577-Gene Expression Regulation,
pubmed-meshheading:20370577-Humans,
pubmed-meshheading:20370577-Insulin-Like Growth Factor Binding Protein 2,
pubmed-meshheading:20370577-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:20370577-Morpholines,
pubmed-meshheading:20370577-Neoplasms,
pubmed-meshheading:20370577-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20370577-Polymerase Chain Reaction,
pubmed-meshheading:20370577-Promoter Regions, Genetic,
pubmed-meshheading:20370577-Protein Kinases,
pubmed-meshheading:20370577-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20370577-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20370577-RNA, Messenger,
pubmed-meshheading:20370577-Signal Transduction,
pubmed-meshheading:20370577-Sirolimus,
pubmed-meshheading:20370577-Somatomedins,
pubmed-meshheading:20370577-Sp1 Transcription Factor,
pubmed-meshheading:20370577-TOR Serine-Threonine Kinases,
pubmed-meshheading:20370577-Transcription, Genetic
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pubmed:year |
2010
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pubmed:articleTitle |
IGFBP-2 expression in MCF-7 cells is regulated by the PI3K/AKT/mTOR pathway through Sp1-induced increase in transcription.
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pubmed:affiliation |
Departments of Medicine and Oncology, Lady Davis Institute for Medical Research, Montreal SMBD Jewish General Hospital, and McGill University, Montreal, Quebec, CanadaH3T 1E2.
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pubmed:publicationType |
Journal Article
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