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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2003-6-24
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pubmed:abstractText |
In breast cancer cells, 17-beta-estradiol (E2) upregulates the expression of insulin receptor substrate 1 (IRS-1), a molecule transmitting insulin-like growth factor-I (IGF-I) signals through the PI-3K/Akt survival pathways. The stimulation of IRS-1 by E2 has been documented on the transcriptional level. Here we studied whether the expression of estrogen receptor (ER)-alpha affects IRS molecules post-transcriptionally. We used ER-alpha-negative MDA-MB-231 breast cancer cells and MDA-MB-231 cells with re-expressed ER-alpha. In MDA-MB-231 cells cultured under serum-free conditions, IRS-1 and IRS-2 were degraded through the 26S proteasome and calpain pathways. Re-expression of ER-alpha in MDA-MB-231 cells correlated with enhanced stability of IRS molecules. This effect coincided with significantly reduced ubiquitination of IRS-1 and IRS-2, but did not involve increased IRS-1 and IRS-2 transcription. The interference of ER-alpha with IRS-1 and IRS-2 turnover could rely on the competition for common degradation pathways, as in MDA-MB-231/ER cells, ER-alpha processing was blocked by proteasome and calpain inhibitors. Notably, a fraction of the cytosolic ER-alpha colocalized and coprecipitated with IRS-1 and IRS-2, indicating a possible common destination for these proteins. The stabilization of IRS-1 in MDA-MB-231/ER cells was paralleled by the upregulation of the IRS-1/Akt/GSK-3 pathway and improved survival in the presence of IGF-I, whereas IRS-2 was not involved in IGF-I signaling.
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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/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4007-16
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12821935-Blotting, Western,
pubmed-meshheading:12821935-Breast Neoplasms,
pubmed-meshheading:12821935-Cell Division,
pubmed-meshheading:12821935-Cell Survival,
pubmed-meshheading:12821935-Cysteine Endopeptidases,
pubmed-meshheading:12821935-Endoplasmic Reticulum,
pubmed-meshheading:12821935-Estrogen Receptor alpha,
pubmed-meshheading:12821935-Humans,
pubmed-meshheading:12821935-Insulin Receptor Substrate Proteins,
pubmed-meshheading:12821935-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12821935-Ligands,
pubmed-meshheading:12821935-Microscopy, Confocal,
pubmed-meshheading:12821935-Microscopy, Fluorescence,
pubmed-meshheading:12821935-Multienzyme Complexes,
pubmed-meshheading:12821935-Peptide Hydrolases,
pubmed-meshheading:12821935-Phosphoproteins,
pubmed-meshheading:12821935-Precipitin Tests,
pubmed-meshheading:12821935-Proteasome Endopeptidase Complex,
pubmed-meshheading:12821935-Receptors, Estrogen,
pubmed-meshheading:12821935-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12821935-Signal Transduction,
pubmed-meshheading:12821935-Time Factors,
pubmed-meshheading:12821935-Transcription, Genetic,
pubmed-meshheading:12821935-Tumor Cells, Cultured,
pubmed-meshheading:12821935-Ubiquitin
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pubmed:year |
2003
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pubmed:articleTitle |
Estrogen receptor-alpha regulates the degradation of insulin receptor substrates 1 and 2 in breast cancer cells.
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pubmed:affiliation |
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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