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Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors

The purpose of this study was to explore the role of transcription factor Ets1 in estrogen receptor α (ERα)-positive breast cancer progression. We expressed human Ets1 or empty vector in four human ERα-positive breast cancer cell lines and observed increased colony formation. Further examination of...

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Autores principales: Kalet, Brian T., Anglin, Sara R., Handschy, Anne, O’Donoghue, Liza E., Halsey, Charles, Chubb, Laura, Korch, Christopher, Duval, Dawn L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706316/
https://www.ncbi.nlm.nih.gov/pubmed/23874775
http://dx.doi.org/10.1371/journal.pone.0068815
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author Kalet, Brian T.
Anglin, Sara R.
Handschy, Anne
O’Donoghue, Liza E.
Halsey, Charles
Chubb, Laura
Korch, Christopher
Duval, Dawn L.
author_facet Kalet, Brian T.
Anglin, Sara R.
Handschy, Anne
O’Donoghue, Liza E.
Halsey, Charles
Chubb, Laura
Korch, Christopher
Duval, Dawn L.
author_sort Kalet, Brian T.
collection PubMed
description The purpose of this study was to explore the role of transcription factor Ets1 in estrogen receptor α (ERα)-positive breast cancer progression. We expressed human Ets1 or empty vector in four human ERα-positive breast cancer cell lines and observed increased colony formation. Further examination of cellular responses in stable Ets1-expressing MCF7 clones displayed increased proliferation, migration, and invasion. Ets1-expressing MCF7 tumors grown in the mammary fat pads of nude mice exhibited increased rates of tumor growth (7.36±2.47 mm(3)/day) compared to control MCF7 tumors (2.52±1.70 mm(3)/day), but maintained their dependence on estradiol for tumor growth. Proliferation marker Ki-67 staining was not different between control and Ets1-expressing tumors, but Ets1-expressing tumors exhibited large necrotic centers and elevated apoptotic staining. Ets1 was shown to cooperate with ERα and the p160 nuclear receptor coactivator (NCOA/SRC) family to increase activation of a consensus estrogen response element luciferase reporter construct. Ets1-expressing MCF7 cells also exhibited elevated expression of the ERα target genes, progesterone receptor and trefoil factor 1. Using GST-pulldown assays, Ets1 formed stable complexes containing both ERα and p160 nuclear receptor coactivators. Taken together, these data suggest that the Ets1-dependent estradiol sensitization of breast cancer cells and tumors may be partially due to the ability of Ets1 to cooperate with ERα and nuclear receptor coactivators to stimulate transcriptional activity of estrogen-dependent genes.
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spelling pubmed-37063162013-07-19 Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors Kalet, Brian T. Anglin, Sara R. Handschy, Anne O’Donoghue, Liza E. Halsey, Charles Chubb, Laura Korch, Christopher Duval, Dawn L. PLoS One Research Article The purpose of this study was to explore the role of transcription factor Ets1 in estrogen receptor α (ERα)-positive breast cancer progression. We expressed human Ets1 or empty vector in four human ERα-positive breast cancer cell lines and observed increased colony formation. Further examination of cellular responses in stable Ets1-expressing MCF7 clones displayed increased proliferation, migration, and invasion. Ets1-expressing MCF7 tumors grown in the mammary fat pads of nude mice exhibited increased rates of tumor growth (7.36±2.47 mm(3)/day) compared to control MCF7 tumors (2.52±1.70 mm(3)/day), but maintained their dependence on estradiol for tumor growth. Proliferation marker Ki-67 staining was not different between control and Ets1-expressing tumors, but Ets1-expressing tumors exhibited large necrotic centers and elevated apoptotic staining. Ets1 was shown to cooperate with ERα and the p160 nuclear receptor coactivator (NCOA/SRC) family to increase activation of a consensus estrogen response element luciferase reporter construct. Ets1-expressing MCF7 cells also exhibited elevated expression of the ERα target genes, progesterone receptor and trefoil factor 1. Using GST-pulldown assays, Ets1 formed stable complexes containing both ERα and p160 nuclear receptor coactivators. Taken together, these data suggest that the Ets1-dependent estradiol sensitization of breast cancer cells and tumors may be partially due to the ability of Ets1 to cooperate with ERα and nuclear receptor coactivators to stimulate transcriptional activity of estrogen-dependent genes. Public Library of Science 2013-07-09 /pmc/articles/PMC3706316/ /pubmed/23874775 http://dx.doi.org/10.1371/journal.pone.0068815 Text en © 2013 Kalet et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kalet, Brian T.
Anglin, Sara R.
Handschy, Anne
O’Donoghue, Liza E.
Halsey, Charles
Chubb, Laura
Korch, Christopher
Duval, Dawn L.
Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors
title Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors
title_full Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors
title_fullStr Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors
title_full_unstemmed Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors
title_short Transcription Factor Ets1 Cooperates with Estrogen Receptor α to Stimulate Estradiol-Dependent Growth in Breast Cancer Cells and Tumors
title_sort transcription factor ets1 cooperates with estrogen receptor α to stimulate estradiol-dependent growth in breast cancer cells and tumors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706316/
https://www.ncbi.nlm.nih.gov/pubmed/23874775
http://dx.doi.org/10.1371/journal.pone.0068815
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