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Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer

INTRODUCTION: The impact of interactions between the two estrogen receptor (ER) subtypes, ERα and ERβ, on gene expression in breast cancer biology is not clear. The goal of this study was to examine transcriptomic alterations in cancer cells co-expressing both receptors and the association of gene e...

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Autores principales: Lin, Chin-Yo, Ström, Anders, Li Kong, Say, Kietz, Silke, Thomsen, Jane S, Tee, Jason BS, Vega, Vinsensius B, Miller, Lance D, Smeds, Johanna, Bergh, Jonas, Gustafsson, Jan-Åke, Liu, Edison T
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868918/
https://www.ncbi.nlm.nih.gov/pubmed/17428314
http://dx.doi.org/10.1186/bcr1667
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author Lin, Chin-Yo
Ström, Anders
Li Kong, Say
Kietz, Silke
Thomsen, Jane S
Tee, Jason BS
Vega, Vinsensius B
Miller, Lance D
Smeds, Johanna
Bergh, Jonas
Gustafsson, Jan-Åke
Liu, Edison T
author_facet Lin, Chin-Yo
Ström, Anders
Li Kong, Say
Kietz, Silke
Thomsen, Jane S
Tee, Jason BS
Vega, Vinsensius B
Miller, Lance D
Smeds, Johanna
Bergh, Jonas
Gustafsson, Jan-Åke
Liu, Edison T
author_sort Lin, Chin-Yo
collection PubMed
description INTRODUCTION: The impact of interactions between the two estrogen receptor (ER) subtypes, ERα and ERβ, on gene expression in breast cancer biology is not clear. The goal of this study was to examine transcriptomic alterations in cancer cells co-expressing both receptors and the association of gene expression signatures with disease outcome. METHODS: Transcriptional effects of ERβ overexpression were determined in a stably transfected cell line derived from ERα-positive T-47D cells. Microarray analysis was carried out to identify differential gene expression in the cell line, and expression of key genes was validated by quantitative polymerase chain reaction. Microarray and clinical data from patient samples were then assessed to determine the in vivo relevance of the expression profiles observed in the cell line. RESULTS: A subset of 14 DNA replication and cell cycle-related genes was found to be specifically downregulated by ERβ. Expression profiles of four genes, CDC2, CDC6, CKS2, and DNA2L, were significantly inversely correlated with ERβ transcript levels in patient samples, consistent with in vitro observations. Kaplan-Meier analysis revealed better disease outcome for the patient group with an expression signature linked to higher ERβ expression as compared to the lower ERβ-expressing group for both disease-free survival (p = 0.00165) and disease-specific survival (p = 0.0268). These findings were further validated in an independent cohort. CONCLUSION: Our findings revealed a transcriptionally regulated mechanism for the previously described growth inhibitory effects of ERβ in ERα-positive breast tumor cells and provide evidence for a functional and beneficial impact of ERβ in primary breast tumors.
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spelling pubmed-18689182007-05-16 Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer Lin, Chin-Yo Ström, Anders Li Kong, Say Kietz, Silke Thomsen, Jane S Tee, Jason BS Vega, Vinsensius B Miller, Lance D Smeds, Johanna Bergh, Jonas Gustafsson, Jan-Åke Liu, Edison T Breast Cancer Res Research Article INTRODUCTION: The impact of interactions between the two estrogen receptor (ER) subtypes, ERα and ERβ, on gene expression in breast cancer biology is not clear. The goal of this study was to examine transcriptomic alterations in cancer cells co-expressing both receptors and the association of gene expression signatures with disease outcome. METHODS: Transcriptional effects of ERβ overexpression were determined in a stably transfected cell line derived from ERα-positive T-47D cells. Microarray analysis was carried out to identify differential gene expression in the cell line, and expression of key genes was validated by quantitative polymerase chain reaction. Microarray and clinical data from patient samples were then assessed to determine the in vivo relevance of the expression profiles observed in the cell line. RESULTS: A subset of 14 DNA replication and cell cycle-related genes was found to be specifically downregulated by ERβ. Expression profiles of four genes, CDC2, CDC6, CKS2, and DNA2L, were significantly inversely correlated with ERβ transcript levels in patient samples, consistent with in vitro observations. Kaplan-Meier analysis revealed better disease outcome for the patient group with an expression signature linked to higher ERβ expression as compared to the lower ERβ-expressing group for both disease-free survival (p = 0.00165) and disease-specific survival (p = 0.0268). These findings were further validated in an independent cohort. CONCLUSION: Our findings revealed a transcriptionally regulated mechanism for the previously described growth inhibitory effects of ERβ in ERα-positive breast tumor cells and provide evidence for a functional and beneficial impact of ERβ in primary breast tumors. BioMed Central 2007 2007-04-10 /pmc/articles/PMC1868918/ /pubmed/17428314 http://dx.doi.org/10.1186/bcr1667 Text en Copyright © 2007 Lin et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lin, Chin-Yo
Ström, Anders
Li Kong, Say
Kietz, Silke
Thomsen, Jane S
Tee, Jason BS
Vega, Vinsensius B
Miller, Lance D
Smeds, Johanna
Bergh, Jonas
Gustafsson, Jan-Åke
Liu, Edison T
Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
title Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
title_full Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
title_fullStr Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
title_full_unstemmed Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
title_short Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
title_sort inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868918/
https://www.ncbi.nlm.nih.gov/pubmed/17428314
http://dx.doi.org/10.1186/bcr1667
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