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Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer

The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-α and ER-β. Although ER-α has been well characterized, the role of ER-β as a prognostic indicator remains unresolved. To determin...

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Autores principales: Myers, E, Fleming, F J, Crotty, T B, Kelly, G, McDermott, E W, O'Higgins, N J, Hill, A D K, Young, L S
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409954/
https://www.ncbi.nlm.nih.gov/pubmed/15477868
http://dx.doi.org/10.1038/sj.bjc.6602156
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author Myers, E
Fleming, F J
Crotty, T B
Kelly, G
McDermott, E W
O'Higgins, N J
Hill, A D K
Young, L S
author_facet Myers, E
Fleming, F J
Crotty, T B
Kelly, G
McDermott, E W
O'Higgins, N J
Hill, A D K
Young, L S
author_sort Myers, E
collection PubMed
description The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-α and ER-β. Although ER-α has been well characterized, the role of ER-β as a prognostic indicator remains unresolved. To determine isoform-specific expression of ER and coexpression with activator proteins, we examined the expression and localisation of ER-α, ER-β and the coactivator protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and immunofluorescence in a cohort of human breast cancer patients (n=150). Relative levels of SRC-1 in primary breast cultures derived from patient tumours in the presence of β-oestradiol and tamoxifen was assessed using Western blotting (n=14). Oestrogen receptor-β protein expression was associated with disease-free survival (DFS) and inversely associated with the expression of HER2 (P=0.0008 and P<0.0001, respectively), whereas SRC-1 was negatively associated with DFS and positively correlated with HER2 (P<0.0001 and P<0.0001, respectively). Steroid receptor coactivator 1 protein expression was regulated in response to β-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-β and SRC-1 was inversely associated (P=0.0001). The association of ER-β protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer.
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spelling pubmed-24099542009-09-10 Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer Myers, E Fleming, F J Crotty, T B Kelly, G McDermott, E W O'Higgins, N J Hill, A D K Young, L S Br J Cancer Molecular and Cellular Pathology The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-α and ER-β. Although ER-α has been well characterized, the role of ER-β as a prognostic indicator remains unresolved. To determine isoform-specific expression of ER and coexpression with activator proteins, we examined the expression and localisation of ER-α, ER-β and the coactivator protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and immunofluorescence in a cohort of human breast cancer patients (n=150). Relative levels of SRC-1 in primary breast cultures derived from patient tumours in the presence of β-oestradiol and tamoxifen was assessed using Western blotting (n=14). Oestrogen receptor-β protein expression was associated with disease-free survival (DFS) and inversely associated with the expression of HER2 (P=0.0008 and P<0.0001, respectively), whereas SRC-1 was negatively associated with DFS and positively correlated with HER2 (P<0.0001 and P<0.0001, respectively). Steroid receptor coactivator 1 protein expression was regulated in response to β-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-β and SRC-1 was inversely associated (P=0.0001). The association of ER-β protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer. Nature Publishing Group 2004-11-01 2004-10-12 /pmc/articles/PMC2409954/ /pubmed/15477868 http://dx.doi.org/10.1038/sj.bjc.6602156 Text en Copyright © 2004 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular and Cellular Pathology
Myers, E
Fleming, F J
Crotty, T B
Kelly, G
McDermott, E W
O'Higgins, N J
Hill, A D K
Young, L S
Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
title Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
title_full Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
title_fullStr Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
title_full_unstemmed Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
title_short Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
title_sort inverse relationship between er-β and src-1 predicts outcome in endocrine-resistant breast cancer
topic Molecular and Cellular Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409954/
https://www.ncbi.nlm.nih.gov/pubmed/15477868
http://dx.doi.org/10.1038/sj.bjc.6602156
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