Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice

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dc.rights.license https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ es_ES
dc.creator Zubeldía-Brenner, Lautaro es_ES
dc.creator De Winne, Catalina es_ES
dc.creator Perrone, Sofía es_ES
dc.creator Rodríguez-Seguí, Santiago A es_ES
dc.creator Willems, Christophe es_ES
dc.creator Ornstein, Ana María es_ES
dc.creator Lacau-Mengido, Isabel es_ES
dc.creator Vankelecom, Hugo es_ES
dc.creator Cristina, Carolina es_ES
dc.creator Becu-Villalobos, Damasia es_ES
dc.date.accessioned 2021-02-03T14:19:56Z
dc.date.available 2021-02-03T14:19:56Z
dc.date.issued 2018-08-18
dc.identifier.citation Zubeldía-Brenner L, De Winne C, Perrone S, Rodríguez-Seguí SA, Willems C, Ornstein AM, Lacau-Mengido I, Vankelecom H, Cristina C, Becu-Villalobos D. Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice. Endocr Relat Cancer. 2019 Jan 1;26(1):13-29. doi: 10.1530/ERC-18-0337. PMID: 30121620. es_ES
dc.identifier.issn 1479-6821 es_ES
dc.identifier.issn 1351-0088 es_ES
dc.identifier.uri http://repositorio.unnoba.edu.ar:8080/xmlui/handle/23601/112
dc.description.abstract Preclinical and clinical studies support that Notch signaling may play an important oncogenic role in cancer, but there is scarce information for pituitary tumors. We therefore undertook a functional study to evaluate Notch participation in pituitary adenoma growth. Tumors generated in Nude mice by subcutaneous GH3 somatolactotrope cell injection were treated in vivo with DAPT, a γ-secretase inhibitor, thus inactivating Notch signaling. This treatment led to pituitary tumor reduction, lower prolactin and GH tumor content and a decrease in angiogenesis. Furthermore, in silico transcriptomic and epigenomic analyses uncovered several tumor suppressor genes related to Notch signaling in pituitary tissue, namely Btg2, Nr4a1, Men1, Zfp36 and Cnot1. Gene evaluation suggested that Btg2, Nr4a1 and Cnot1 may be possible players in GH3 xenograft growth. Btg2 mRNA expression was lower in GH3 tumors compared to the parental line, and DAPT increased its expression levels in the tumor in parallel with the inhibition of its volume. Cnot1 mRNA levels were also increased in the pituitary xenografts by DAPT treatment. And the Nr4a1 gene was lower in tumors compared to the parental line, though not modified by DAPT. Finally, because DAPT in vivo may also be acting on tumor microenvironment, we determined the direct effect of DAPT on GH3 cells in vitro. We found that DAPT decreases the proliferative, secretory and migration potential of GH3 cells. These results position selective interruption of Notch signaling as a potential therapeutic tool in adjuvant treatments for aggressive or resistant pituitary tumors. es_ES
dc.description.sponsorship Fil: Zubeldía-Brenner, Lautaro. Universidad de Buenos Aires (UBA). Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. es_ES
dc.description.sponsorship Fil: De Winne, Catalina. Universidad de Buenos Aires (UBA). Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. es_ES
dc.description.sponsorship Fil: Perrone, Sofía. Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA). CIT NOBA (UNNOBA-UNSADA-CONICET). Centro de Investigaciones Básicas y Aplicadas (CIBA). Laboratorio de Fisiopatología de la Hipófisis; Argentina. es_ES
dc.description.sponsorship Fil: Rodríguez-Seguí, Santiago A. Universidad de Buenos Aires (UBA). Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología y Biología Molecular y Celular. CONICET-UBA. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE); Argentina. es_ES
dc.description.sponsorship Fil: Willems, Christophe. KU Leuven (University of Leuven). Department of Development and Regeneration, Cluster Stem Cell and Developmental Biology, Unit of Stem Cell Research; Belgium. es_ES
dc.description.sponsorship Fil: Ornstein, Ana María. Universidad de Buenos Aires (UBA). Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. es_ES
dc.description.sponsorship Fil: Lacau-Mengido, Isabel. Universidad de Buenos Aires (UBA). Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. es_ES
dc.description.sponsorship Fil: Vankelecom, Hugo. KU Leuven (University of Leuven). Department of Development and Regeneration, Cluster Stem Cell and Developmental Biology, Unit of Stem Cell Research; Belgium. es_ES
dc.description.sponsorship Fil: Cristina, Carolina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA). CIT NOBA (UNNOBA-UNSADA-CONICET). Centro de Investigaciones Básicas y Aplicadas (CIBA). Laboratorio de Fisiopatología de la Hipófisis; Argentina. es_ES
dc.description.sponsorship Fil: Becu-Villalobos, Damasia. Universidad de Buenos Aires (UBA). Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. es_ES
dc.format application/pdf es_ES
dc.language.iso eng es_ES
dc.publisher Bioscientifica es_ES
dc.rights info:eu-repo/semantics/openAccess es_ES
dc.source Endocrine-Related Cancer es_ES
dc.subject DAPT es_ES
dc.subject Pituitary es_ES
dc.subject Angiogenesis es_ES
dc.subject Prolactin es_ES
dc.subject GH es_ES
dc.title Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:ar-repo/semantics/artículo es_ES
dc.type info:eu-repo/semantics/publishedVersion es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:ar-repo/semantics/artículo es_ES
dc.type info:eu-repo/semantics/publishedVersion es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:ar-repo/semantics/artículo es_ES
dc.type info:eu-repo/semantics/publishedVersion es_ES
dc.description.version Con referato es_ES
dc.relation.publisherversion https://doi.org/10.1530/ERC-18-0337 es_ES
dc.contributor.orcid https://orcid.org/0000-0002-5641-3109 es_ES
dc.contributor.orcid https://orcid.org/0000-0003-3161-7305 es_ES
dc.contributor.orcid https://orcid.org/0000-0002-5732-2604 es_ES
dc.contributor.orcid https://orcid.org/0000-0003-2547-3819 es_ES
dc.contributor.orcid https://orcid.org/0000-0002-2251-7284 es_ES
dc.contributor.orcid https://orcid.org/0000-0003-2952-8485 es_ES


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