The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships

Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E.

Risultato della ricerca: Article

15 Citazioni (Scopus)

Abstract

Background: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor a (ERa) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERa, translocates to the nucleus, and modulates ERa-dependent transcription at estrogen response elements (ERE). Here, we studied structure–function relationships of the ERa:IRS-1 complex under IGF-1 and/or estradiol (E2) stimulation. Materials and methods: ERa and IRS-1 deletion mutants were used to analyze structural and functional ERa/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERa-dependent ERE transcription was examined by chromatin immunoprecipitation and gene reporter analysis, respectively. The requirement for IRS-1 in ERa function was tested with RNAi technology. Results: Nuclear translocation of IRS-1 was induced by E2, IGF-1, and a combination of both stimuli. ERa/IRS-1 binding was direct and involved the activation function-1 (AF-1)/DNA binding domain (DBD) region of ERa and two discrete regions of IRS-1 (the N-terminal pleckstrin homology domain and a region within the C-terminus). IRS-1 knock down abrogated IGF-1-dependent transcriptional activity of unliganded ERa, but induced the activity of liganded ERa. Conclusions: ERa/IRS-1 interactions are direct and involve the ERa AF-1/DBD domain and IRS-1 domains mapping within N- and C-terminus. IRS-1 may act as a repressor of liganded ERa and coactivator of unliganded ERa.
Lingua originaleEnglish
pagine (da-a)81-85
Numero di pagine5
RivistaAnnals of Oncology
Volume18
Stato di pubblicazionePublished - 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research
  • Hematology

Cita questo

Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E. (2007). The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships. Annals of Oncology, 18, 81-85.

The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships. / Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E.

In: Annals of Oncology, Vol. 18, 2007, pag. 81-85.

Risultato della ricerca: Article

Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E. 2007, 'The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships', Annals of Oncology, vol. 18, pagg. 81-85.
Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E. The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships. Annals of Oncology. 2007;18:81-85.
Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E. / The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships. In: Annals of Oncology. 2007 ; Vol. 18. pagg. 81-85.
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title = "The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships",
abstract = "Background: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor a (ERa) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERa, translocates to the nucleus, and modulates ERa-dependent transcription at estrogen response elements (ERE). Here, we studied structure–function relationships of the ERa:IRS-1 complex under IGF-1 and/or estradiol (E2) stimulation. Materials and methods: ERa and IRS-1 deletion mutants were used to analyze structural and functional ERa/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERa-dependent ERE transcription was examined by chromatin immunoprecipitation and gene reporter analysis, respectively. The requirement for IRS-1 in ERa function was tested with RNAi technology. Results: Nuclear translocation of IRS-1 was induced by E2, IGF-1, and a combination of both stimuli. ERa/IRS-1 binding was direct and involved the activation function-1 (AF-1)/DNA binding domain (DBD) region of ERa and two discrete regions of IRS-1 (the N-terminal pleckstrin homology domain and a region within the C-terminus). IRS-1 knock down abrogated IGF-1-dependent transcriptional activity of unliganded ERa, but induced the activity of liganded ERa. Conclusions: ERa/IRS-1 interactions are direct and involve the ERa AF-1/DBD domain and IRS-1 domains mapping within N- and C-terminus. IRS-1 may act as a repressor of liganded ERa and coactivator of unliganded ERa.",
author = "{Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E.} and Antonio Russo and Sandra Cascio",
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T1 - The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships

AU - Sisci, D.; Morelli, C.; Lanzino, M.; Garofalo, C.; Reiss, K.; Garcia, M.; A, ; Ando, S.; Surmacz, E.

AU - Russo, Antonio

AU - Cascio, Sandra

PY - 2007

Y1 - 2007

N2 - Background: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor a (ERa) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERa, translocates to the nucleus, and modulates ERa-dependent transcription at estrogen response elements (ERE). Here, we studied structure–function relationships of the ERa:IRS-1 complex under IGF-1 and/or estradiol (E2) stimulation. Materials and methods: ERa and IRS-1 deletion mutants were used to analyze structural and functional ERa/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERa-dependent ERE transcription was examined by chromatin immunoprecipitation and gene reporter analysis, respectively. The requirement for IRS-1 in ERa function was tested with RNAi technology. Results: Nuclear translocation of IRS-1 was induced by E2, IGF-1, and a combination of both stimuli. ERa/IRS-1 binding was direct and involved the activation function-1 (AF-1)/DNA binding domain (DBD) region of ERa and two discrete regions of IRS-1 (the N-terminal pleckstrin homology domain and a region within the C-terminus). IRS-1 knock down abrogated IGF-1-dependent transcriptional activity of unliganded ERa, but induced the activity of liganded ERa. Conclusions: ERa/IRS-1 interactions are direct and involve the ERa AF-1/DBD domain and IRS-1 domains mapping within N- and C-terminus. IRS-1 may act as a repressor of liganded ERa and coactivator of unliganded ERa.

AB - Background: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor a (ERa) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERa, translocates to the nucleus, and modulates ERa-dependent transcription at estrogen response elements (ERE). Here, we studied structure–function relationships of the ERa:IRS-1 complex under IGF-1 and/or estradiol (E2) stimulation. Materials and methods: ERa and IRS-1 deletion mutants were used to analyze structural and functional ERa/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERa-dependent ERE transcription was examined by chromatin immunoprecipitation and gene reporter analysis, respectively. The requirement for IRS-1 in ERa function was tested with RNAi technology. Results: Nuclear translocation of IRS-1 was induced by E2, IGF-1, and a combination of both stimuli. ERa/IRS-1 binding was direct and involved the activation function-1 (AF-1)/DNA binding domain (DBD) region of ERa and two discrete regions of IRS-1 (the N-terminal pleckstrin homology domain and a region within the C-terminus). IRS-1 knock down abrogated IGF-1-dependent transcriptional activity of unliganded ERa, but induced the activity of liganded ERa. Conclusions: ERa/IRS-1 interactions are direct and involve the ERa AF-1/DBD domain and IRS-1 domains mapping within N- and C-terminus. IRS-1 may act as a repressor of liganded ERa and coactivator of unliganded ERa.

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