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...

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Autor principal: Zubeldía-Brenner, L.
Otros Autores: De Winne, C., Perrone, S., Rodríguez-Seguí, S.A, Willems, C., Ornstein, A.M, Lacau-Mengido, I., Vankelecom, H., Cristina, C., Becu-Villalobos, D.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: BioScientifica Ltd. 2019
Acceso en línea:Registro en Scopus
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100 1 |a Zubeldía-Brenner, L. 
245 1 0 |a Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice 
260 |b BioScientifica Ltd.  |c 2019 
270 1 0 |m Becu-Villalobos, D.; Instituto de Biología y Medicina Experimental, IBYME-CONICETArgentina; email: dbecu@dna.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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. © 2019 Society for Endocrinology Published by Bioscientifica Ltd.  |l eng 
536 |a Detalles de la financiación: KU Leuven 
536 |a Detalles de la financiación: Universidad Nacional del Centro de la Provincia de Buenos Aires 
536 |a Detalles de la financiación: Universidad Nacional del Centro de la Provincia de Buenos Aires 
536 |a Detalles de la financiación: Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires 
536 |a Detalles de la financiación: Facultad de Ciencias Físicas y Matemáticas 
536 |a Detalles de la financiación: Universidad de Buenos Aires 
536 |a Detalles de la financiación: Fonds Wetenschappelijk Onderzoek 
536 |a Detalles de la financiación: 1Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires, Argentina 2Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires, CITNOBA (UNNOBA-CONICET), Universidad Nacional del Noroeste de la Provincia de Buenos Aires, Buenos Aires, Argentina 3Departamento de Fisiología y Biología Molecular y Celular, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina 4CONICET-Universidad de Buenos Aires, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina 5Department of Development and Regeneration, Cluster Stem Cell and Developmental Biology, Unit of Stem Cell Research, KU Leuven (University of Leuven), Leuven, Belgium 
536 |a Detalles de la financiación: grant between M 阀NCYT and Fund for Scientific Research (FWO) – Flanders 
593 |a Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires, Argentina 
593 |a Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires, CITNOBA (UNNOBA-CONICET), Universidad Nacional delNoroeste de la Provincia de Buenos Aires, Buenos Aires, Argentina 
593 |a Departamento de Fisiología y Biología Molecular y Celular, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina 
593 |a CONICET-Universidad de Buenos Aires, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina 
593 |a Department of Development and Regeneration, Cluster Stem Cell and Developmental Biology, Unit of Stem Cell Research, KU Leuven (University of Leuven), Leuven, Belgium 
690 1 0 |a ANGIOGENESIS 
690 1 0 |a DAPT 
690 1 0 |a GH 
690 1 0 |a PITUITARY 
690 1 0 |a PROLACTIN 
690 1 0 |a GROWTH HORMONE 
690 1 0 |a MESSENGER RNA 
690 1 0 |a NOTCH RECEPTOR 
690 1 0 |a PROLACTIN 
690 1 0 |a ANGIOGENESIS 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ARTICLE 
690 1 0 |a BTG2 GENE 
690 1 0 |a CANCER INHIBITION 
690 1 0 |a CARCINOGENESIS 
690 1 0 |a CELL MIGRATION 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a CELLULAR SECRETION 
690 1 0 |a CNOT1 GENE 
690 1 0 |a COMPUTER MODEL 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DISEASE ASSOCIATION 
690 1 0 |a EPIGENETICS 
690 1 0 |a GH3 CELL LINE 
690 1 0 |a HYPOPHYSIS ADENOMA 
690 1 0 |a IN VITRO STUDY 
690 1 0 |a IN VIVO STUDY 
690 1 0 |a MOUSE 
690 1 0 |a MRNA EXPRESSION LEVEL 
690 1 0 |a NONHUMAN 
690 1 0 |a NOTCH SIGNALING 
690 1 0 |a NR4A1 GENE 
690 1 0 |a RAT 
690 1 0 |a TRANSCRIPTOMICS 
690 1 0 |a TUMOR GROWTH 
690 1 0 |a TUMOR MICROENVIRONMENT 
700 1 |a De Winne, C. 
700 1 |a Perrone, S. 
700 1 |a Rodríguez-Seguí, S.A. 
700 1 |a Willems, C. 
700 1 |a Ornstein, A.M. 
700 1 |a Lacau-Mengido, I. 
700 1 |a Vankelecom, H. 
700 1 |a Cristina, C. 
700 1 |a Becu-Villalobos, D. 
773 0 |d BioScientifica Ltd., 2019  |g v. 26  |h pp. 13-29  |k n. 1  |p Endocr.-Relat. Cancer  |x 13510088  |t Endocrine-Related Cancer 
856 4 1 |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056959998&doi=10.1530%2fERC-18-0337&partnerID=40&md5=ac6726612269356aabc66939418cb83e  |y Registro en Scopus 
856 4 0 |u https://doi.org/10.1530/ERC-18-0337  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_13510088_v26_n1_p13_ZubeldiaBrenner  |y Handle 
856 4 0 |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13510088_v26_n1_p13_ZubeldiaBrenner  |y Registro en la Biblioteca Digital 
961 |a paper_13510088_v26_n1_p13_ZubeldiaBrenner  |b paper  |c PE 
962 |a info:eu-repo/semantics/article  |a info:ar-repo/semantics/artículo  |b info:eu-repo/semantics/publishedVersion 
999 |c 86776