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dc.contributor.author
Wu, Yanming
dc.contributor.author
Zhang, Zhao
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Cenciarini, Mauro Ezequiel
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Proietti Anastasi, Cecilia Jazmín
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Amasino, Matías Federico
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Hong, Tao
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Yang, Mei
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Liao, Yiji
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Chiang, Huai-Chin
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Kaklamani, Virginia G.
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Jeselsohn, Rinath
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Vadlamudi, Ratna K.
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Huang, Tim Hui Ming
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Li, Rong
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De Angelis, Carmine
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Fu, Xiaoyong
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Elizalde, Patricia Virginia
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Schiff, Rachel
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Brown, Myles
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Xu, Kexin
dc.date.available
2021-04-19T04:54:57Z
dc.date.issued
2018-02
dc.identifier.citation
Wu, Yanming; Zhang, Zhao; Cenciarini, Mauro Ezequiel; Proietti Anastasi, Cecilia Jazmín; Amasino, Matías Federico; et al.; Tamoxifen resistance in breast cancer is regulated by the EZH2–ERa–GREB1 transcriptional axis; American Association for Cancer Research; Cancer Research; 78; 3; 2-2018; 671-684
dc.identifier.issn
0008-5472
dc.identifier.uri
http://hdl.handle.net/11336/130301
dc.description.abstract
Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor a (ERa) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG-enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERa cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERa coregulators, converting the antiestrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program. Significance: This study suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program defined within.
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application/pdf
dc.language.iso
eng
dc.publisher
American Association for Cancer Research
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
EZH2
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ERalpha signaling
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DNA methylation
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Tamoxifen resistance
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Epigenetic therapy
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Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Tamoxifen resistance in breast cancer is regulated by the EZH2–ERa–GREB1 transcriptional axis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-12-22T15:43:08Z
dc.journal.volume
78
dc.journal.number
3
dc.journal.pagination
671-684
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Philadelphia
dc.description.fil
Fil: Wu, Yanming. University of Texas at San Antonio; Estados Unidos
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Fil: Zhang, Zhao. University of Texas at San Antonio; Estados Unidos
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Fil: Cenciarini, Mauro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
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Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
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Fil: Amasino, Matías Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
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Fil: Hong, Tao. University of Texas at San Antonio; Estados Unidos. Central South University; China
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Fil: Yang, Mei. University of Texas at San Antonio; Estados Unidos
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Fil: Liao, Yiji. University of Texas at San Antonio; Estados Unidos
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Fil: Chiang, Huai-Chin. University of Texas at San Antonio; Estados Unidos. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;
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Fil: Kaklamani, Virginia G.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;
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Fil: Jeselsohn, Rinath. Dana-farber Cancer Institute; Estados Unidos
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Fil: Vadlamudi, Ratna K.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;
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Fil: Huang, Tim Hui Ming. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;
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Fil: Li, Rong. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;
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Fil: De Angelis, Carmine. Baylor College Of Medicine; Estados Unidos
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Fil: Fu, Xiaoyong. Baylor College Of Medicine; Estados Unidos
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Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
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Fil: Schiff, Rachel. Baylor College Of Medicine; Estados Unidos
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Fil: Brown, Myles. Dana farber Cancer Institute; Estados Unidos
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Fil: Xu, Kexin. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;
dc.journal.title
Cancer Research
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1158/0008-5472.CAN-17-1327
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://cancerres.aacrjournals.org/content/78/3/671
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967248/
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