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Nuclear insulin receptor substrate 1 interacts with estrogen receptor alpha at ERE promoters.
- Source :
-
Oncogene [Oncogene] 2004 Sep 30; Vol. 23 (45), pp. 7517-26. - Publication Year :
- 2004
-
Abstract
- Insulin receptor substrate 1 (IRS-1) is a major signaling molecule activated by the insulin and insulin-like growth factor I receptors. Recent data obtained in different cell models suggested that in addition to its conventional role as a cytoplasmic signal transducer, IRS-1 has a function in the nuclear compartment. However, the role of nuclear IRS-1 in breast cancer has never been addressed. Here we report that in estrogen receptor alpha (ERalpha)-positive MCF-7 cells, (1) a fraction of IRS-1 was translocated to the nucleus upon 17-beta-estradiol (E2) treatment; (2) E2-dependent nuclear translocation of IRS-1 was blocked with the antiestrogen ICI 182,780; (3) nuclear IRS-1 colocalized and co-precipitated with ERalpha; (4) the IRS-1:ERalpha complex was recruited to the E2-sensitive pS2 gene promoter. Notably, IRS-1 interaction with the pS2 promoter did not occur in ERalpha-negative MDA-MB-231 cells, but was observed in MDA-MB-231 cells retransfected with ERalpha. Transcription reporter assays with E2-sensitive promoters suggested that the presence of IRS-1 inhibits ERalpha activity at estrogen-responsive element-containing DNA. In summary, our data suggested that nuclear IRS-1 interacts with ERalpha and that this interaction might influence ERalpha transcriptional activity.
- Subjects :
- Animals
Base Sequence
Blotting, Western
Cell Line, Tumor
DNA Primers
Estrogen Receptor alpha
Humans
Insulin Receptor Substrate Proteins
Precipitin Tests
Protein Binding
Protein Transport
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Phosphoproteins metabolism
Promoter Regions, Genetic
Receptors, Estrogen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 23
- Issue :
- 45
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 15318176
- Full Text :
- https://doi.org/10.1038/sj.onc.1208014