Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant) block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gen...

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Autores principales:	Mathieu Dalvai, Kerstin Bystricky
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1738928a006f4f938ed32e1bb4605d28
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spelling	oai:doaj.org-article:1738928a006f4f938ed32e1bb4605d282021-12-02T20:21:08ZCell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.1932-620310.1371/journal.pone.0011011https://doaj.org/article/1738928a006f4f938ed32e1bb4605d282010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20543978/?tool=EBIhttps://doaj.org/toc/1932-6203Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant) block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7) the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.Mathieu DalvaiKerstin BystrickyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e11011 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mathieu Dalvai Kerstin Bystricky Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.
description	Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant) block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7) the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.
format	article
author	Mathieu Dalvai Kerstin Bystricky
author_facet	Mathieu Dalvai Kerstin Bystricky
author_sort	Mathieu Dalvai
title	Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.
title_short	Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.
title_full	Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.
title_fullStr	Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.
title_full_unstemmed	Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.
title_sort	cell cycle and anti-estrogen effects synergize to regulate cell proliferation and er target gene expression.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/1738928a006f4f938ed32e1bb4605d28
work_keys_str_mv	AT mathieudalvai cellcycleandantiestrogeneffectssynergizetoregulatecellproliferationandertargetgeneexpression AT kerstinbystricky cellcycleandantiestrogeneffectssynergizetoregulatecellproliferationandertargetgeneexpression
_version_	1718374151499022336

Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

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