Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice

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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Zubeldía-Brenner, Lautaro, De Winne, Catalina, Perrone, Sofía, Rodríguez-Seguí, Santiago A, Willems, Christophe, Ornstein, Ana María, Lacau-Mengido, Isabel, Vankelecom, Hugo, Cristina, Carolina, Becu-Villalobos, Damasia
Otros Autores: https://orcid.org/0000-0002-5641-3109
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: Bioscientifica 2021
Materias:
DAPT
Pituitary
Angiogenesis
Prolactin
GH
Acceso en línea:http://repositorio.unnoba.edu.ar:8080/xmlui/handle/23601/112
Aporte de:
Re DI Repositorio Digital UNNOBA de Universidad Nacional del Noroeste de la Provincia de Buenos Aires
id I103-R405-23601-112
record_format dspace
institution Universidad Nacional del Noroeste de la Provincia de Buenos Aires
institution_str I-103
repository_str R-405
collection Re DI Repositorio Digital UNNOBA
language Inglés
topic DAPT
Pituitary
Angiogenesis
Prolactin
GH
spellingShingle DAPT
Pituitary
Angiogenesis
Prolactin
GH
Zubeldía-Brenner, Lautaro
De Winne, Catalina
Perrone, Sofía
Rodríguez-Seguí, Santiago A
Willems, Christophe
Ornstein, Ana María
Lacau-Mengido, Isabel
Vankelecom, Hugo
Cristina, Carolina
Becu-Villalobos, Damasia
Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice
topic_facet DAPT
Pituitary
Angiogenesis
Prolactin
GH
description 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.
author2 https://orcid.org/0000-0002-5641-3109
author_facet https://orcid.org/0000-0002-5641-3109
Zubeldía-Brenner, Lautaro
De Winne, Catalina
Perrone, Sofía
Rodríguez-Seguí, Santiago A
Willems, Christophe
Ornstein, Ana María
Lacau-Mengido, Isabel
Vankelecom, Hugo
Cristina, Carolina
Becu-Villalobos, Damasia
format Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
Artículo
Artículo
publishedVersion
author Zubeldía-Brenner, Lautaro
De Winne, Catalina
Perrone, Sofía
Rodríguez-Seguí, Santiago A
Willems, Christophe
Ornstein, Ana María
Lacau-Mengido, Isabel
Vankelecom, Hugo
Cristina, Carolina
Becu-Villalobos, Damasia
author_sort Zubeldía-Brenner, Lautaro
title Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice
title_short Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice
title_full Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice
title_fullStr Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice
title_full_unstemmed Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice
title_sort inhibition of notch signaling attenuates pituitary adenoma growth in nude mice
publisher Bioscientifica
publishDate 2021
url http://repositorio.unnoba.edu.ar:8080/xmlui/handle/23601/112
work_keys_str_mv AT zubeldiabrennerlautaro inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT dewinnecatalina inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT perronesofia inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT rodriguezseguisantiagoa inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT willemschristophe inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT ornsteinanamaria inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT lacaumengidoisabel inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT vankelecomhugo inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT cristinacarolina inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
AT becuvillalobosdamasia inhibitionofnotchsignalingattenuatespituitaryadenomagrowthinnudemice
_version_ 1850060714671079424
spelling I103-R405-23601-1122025-10-21T21:05:47Z Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice Zubeldía-Brenner, Lautaro De Winne, Catalina Perrone, Sofía Rodríguez-Seguí, Santiago A Willems, Christophe Ornstein, Ana María Lacau-Mengido, Isabel Vankelecom, Hugo Cristina, Carolina Becu-Villalobos, Damasia https://orcid.org/0000-0002-5641-3109 https://orcid.org/0000-0003-3161-7305 https://orcid.org/0000-0002-5732-2604 https://orcid.org/0000-0003-2547-3819 https://orcid.org/0000-0002-2251-7284 https://orcid.org/0000-0003-2952-8485 DAPT Pituitary Angiogenesis Prolactin GH 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. Fil: Zubeldía-Brenner, Lautaro. Universidad de Buenos Aires. Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. Fil: De Winne, Catalina. Universidad de Buenos Aires. Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. Fil: Perrone, Sofía. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. CIT NOBA (UNNOBA-UNSADA-CONICET). Centro de Investigaciones Básicas y Aplicadas. Laboratorio de Fisiopatología de la Hipófisis; Argentina. Fil: Rodríguez-Seguí, Santiago A. Universidad de Buenos Aires. 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. Fil: Willems, Christophe. University of Leuven. Department of Development and Regeneration, Cluster Stem Cell and Developmental Biology, Unit of Stem Cell Research; Belgium. Fil: Ornstein, Ana María. Universidad de Buenos Aires. Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. Fil: Lacau-Mengido, Isabel. Universidad de Buenos Aires. Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. Fil: Vankelecom, Hugo. University of Leuven. Department of Development and Regeneration, Cluster Stem Cell and Developmental Biology, Unit of Stem Cell Research; Belgium. Fil: Cristina, Carolina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. CIT NOBA (UNNOBA-UNSADA-CONICET). Centro de Investigaciones Básicas y Aplicadas . Laboratorio de Fisiopatología de la Hipófisis; Argentina. Fil: Becu-Villalobos, Damasia. Universidad de Buenos Aires. Instituto de Biología y Medicina Experimental (IByME-CONICET). Laboratorio de Regulación Hipofisaria; Argentina. Con referato 2021-02-03T14:19:56Z 2021-02-03T14:19:56Z 2018-08-18 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion 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. 1479-6821 1351-0088 http://repositorio.unnoba.edu.ar:8080/xmlui/handle/23601/112 eng https://doi.org/10.1530/ERC-18-0337 info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf application/pdf Bioscientifica Endocrine-Related Cancer

Ejemplares similares