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Stat3 enhances transactivation of steroid hormone receptors

BACKGROUND: Steroid hormone receptors (SHRs) are members of the superfamily of ligand-activated transcription factors that regulate many biological processes. Co-regulators act as bridging molecules between the SHR and general transcription factors to enhance transactivation of target genes. Previou...

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Detalles Bibliográficos
Autores principales: de Miguel, Fernando, Lee, Soo Ok, Onate, Sergio A, Gao, Allen C
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC179876/
https://www.ncbi.nlm.nih.gov/pubmed/12904256
http://dx.doi.org/10.1186/1478-1336-1-3
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author de Miguel, Fernando
Lee, Soo Ok
Onate, Sergio A
Gao, Allen C
author_facet de Miguel, Fernando
Lee, Soo Ok
Onate, Sergio A
Gao, Allen C
author_sort de Miguel, Fernando
collection PubMed
description BACKGROUND: Steroid hormone receptors (SHRs) are members of the superfamily of ligand-activated transcription factors that regulate many biological processes. Co-regulators act as bridging molecules between the SHR and general transcription factors to enhance transactivation of target genes. Previous studies demonstrated that Stat3 is constitutively activated in prostate cancer and can enhance prostate specific antigen (PSA) expression and promote androgen independent growth. In this study, we investigate whether Stat3 can enhance steroid hormone receptors activation. METHODS: CV-1 cells in which plasmids expressing androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR) or estrogen receptor (ER) were cotransfected with a constitutively active STAT3 mutant. RESULTS: Stat3 stimulates the transcriptional activity of all four SHR tested, AR, GR, PR and ER, in a hormone-dependent manner. Stat3 acts in a synergistic fashion with other coactivators such as SRC-1, pCAF, CBP, and TIF-2 on the transcriptional activity of these SHR. In addition, Stat3 significantly enhanced the sensitivity of androgen receptor in response to androgen. STAT3 did not affect the specificity of AR for other steroid hormones other than androgen or binding of AR to other hormone responsive elements. CONCLUSIONS: These findings suggest that Stat3 can enhance the transactivation of AR, GR, PR and ER, and activated Stat3 could have a role in the development or progression of a hypersensitive AR.
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spelling pubmed-1798762003-08-20 Stat3 enhances transactivation of steroid hormone receptors de Miguel, Fernando Lee, Soo Ok Onate, Sergio A Gao, Allen C Nucl Recept Research BACKGROUND: Steroid hormone receptors (SHRs) are members of the superfamily of ligand-activated transcription factors that regulate many biological processes. Co-regulators act as bridging molecules between the SHR and general transcription factors to enhance transactivation of target genes. Previous studies demonstrated that Stat3 is constitutively activated in prostate cancer and can enhance prostate specific antigen (PSA) expression and promote androgen independent growth. In this study, we investigate whether Stat3 can enhance steroid hormone receptors activation. METHODS: CV-1 cells in which plasmids expressing androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR) or estrogen receptor (ER) were cotransfected with a constitutively active STAT3 mutant. RESULTS: Stat3 stimulates the transcriptional activity of all four SHR tested, AR, GR, PR and ER, in a hormone-dependent manner. Stat3 acts in a synergistic fashion with other coactivators such as SRC-1, pCAF, CBP, and TIF-2 on the transcriptional activity of these SHR. In addition, Stat3 significantly enhanced the sensitivity of androgen receptor in response to androgen. STAT3 did not affect the specificity of AR for other steroid hormones other than androgen or binding of AR to other hormone responsive elements. CONCLUSIONS: These findings suggest that Stat3 can enhance the transactivation of AR, GR, PR and ER, and activated Stat3 could have a role in the development or progression of a hypersensitive AR. BioMed Central 2003-06-13 /pmc/articles/PMC179876/ /pubmed/12904256 http://dx.doi.org/10.1186/1478-1336-1-3 Text en Copyright © 2003 de Miguel et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research
de Miguel, Fernando
Lee, Soo Ok
Onate, Sergio A
Gao, Allen C
Stat3 enhances transactivation of steroid hormone receptors
title Stat3 enhances transactivation of steroid hormone receptors
title_full Stat3 enhances transactivation of steroid hormone receptors
title_fullStr Stat3 enhances transactivation of steroid hormone receptors
title_full_unstemmed Stat3 enhances transactivation of steroid hormone receptors
title_short Stat3 enhances transactivation of steroid hormone receptors
title_sort stat3 enhances transactivation of steroid hormone receptors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC179876/
https://www.ncbi.nlm.nih.gov/pubmed/12904256
http://dx.doi.org/10.1186/1478-1336-1-3
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