Tamoxifen resistance in breast cancer is regulated by the EZH2–ERa–GREB1 transcriptional axis

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.Fil: Wu, Yanming. University of Texas at San Antonio; Estados UnidosFil: Zhang, Zhao. University of Texas at San Antonio; Estados UnidosFil: 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: Hong, Tao. University of Texas at San Antonio; Estados Unidos. Central South University; ChinaFil: Yang, Mei. University of Texas at San Antonio; Estados UnidosFil: Liao, Yiji. University of Texas at San Antonio; Estados UnidosFil: 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;Fil: Kaklamani, Virginia G.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Jeselsohn, Rinath. Dana-farber Cancer Institute; Estados UnidosFil: Vadlamudi, Ratna K.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Huang, Tim Hui Ming. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Li, Rong. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: De Angelis, Carmine. Baylor College Of Medicine; Estados UnidosFil: Fu, Xiaoyong. Baylor College Of Medicine; Estados UnidosFil: 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; ArgentinaFil: Schiff, Rachel. Baylor College Of Medicine; Estados UnidosFil: Brown, Myles. Dana farber Cancer Institute; Estados UnidosFil: Xu, Kexin. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio

Zoonosis por Hantavirus

Las zoonosis por Hantavirus son enfermedades zoonóticas, transmitidas al hombre desde los roedores (ratones y ratas) que portan asintomáticamente el virus y al cual eliminan principalmente por la orina, caracterizadas por fiebre, hipotensión, afección hemorrágica y renal (Fiebre hemorrágica con síndrome renal FHSR) o fiebre, mialgias, malestar, hipoxemia y posible edema pulmonar intenso y brusco, insuficiencia respiratoria y muerte (Síndrome pulmonar por Hantavirus SPH) producida por especies del Género Hantavirus.Facultad de Ciencias Veterinaria