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Artículo

Pivotal role of NF-κB in cellular senescence of experimental pituitary tumours

Mongi Bragato, Bethania del CarmenIcon ; Grondona, EzequielIcon ; Sosa, Liliana del ValleIcon ; Zlocowski, NatachaIcon ; Venier, Ana Clara; Torres, Alicia InesIcon ; Latini, Alexandra; Bainy Leal, Rodrigo; Gutiérrez, SilvinaIcon ; de Paul, Ana LuciaIcon
Fecha de publicación: 05/2020
Editorial: BioScientifica
Revista: Journal of Endocrinology
ISSN: 0022-0795
e-ISSN: 1479-6805
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

The molecular mechanisms underlying the capability of pituitary tumours to avoid unregulated cell proliferation are still not well understood. However, the NF-κB transcription factor, which is able to modulate not only cellular senescence but also tumour progression, has emerged as a targeted candidate. This work was focused on the NF-κB role in cellular senescence during the progression of experimental pituitary tumours. Also, the contribution of the signalling pathways in senescence-associated NF-κB activation and the senescence-associated secretory phenotype (SASP) and pro-survival-NF-κB target genes transcription were analysed. A robust NF-κB activation was seen at E20-E40 of tumour development accompanied by a marked SA-β-Gal co-reactivity in the tumour pituitary parenchyma. The induction of TNFα and IL1-β as specific SASP-related NF-κB target genes as well as Bcl-2 and Bcl-xl pro-survival genes was shown to be accompanied by increases in the p-p38 MAPK protein levels, starting at the E20 stage and strengthening from 40 to 60 days of tumour growth. It is noteworthy that p-JNK displayed a similar pattern of activation during pituitary tumour development, while p-AKT and p-ERK1/2 were downregulated. By employing a pharmacological strategy to abrogate NF-κB activity, we demonstrated a marked reduction in SA-β-Gal activity and a slight decrease in Ki67 immunopositive cells after NF-κB blockade. These results suggest a central role for NF-κB in the regulation of the cellular senescence programme, leading to the strikingly benign intrinsic nature of pituitary adenomas.
Palabras clave: NF-ΚB , PITUITARY TUMOUR , PROLIFERATION , SA-B-GAL , SENESCENCE
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/140524
DOI: http://dx.doi.org/10.1530/JOE-19-0506
URL: https://joe.bioscientifica.com/view/journals/joe/245/2/JOE-19-0506.xml
Colecciones
Articulos(INICSA)
Articulos de INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Citación
Mongi Bragato, Bethania del Carmen; Grondona, Ezequiel; Sosa, Liliana del Valle; Zlocowski, Natacha; Venier, Ana Clara; et al.; Pivotal role of NF-κB in cellular senescence of experimental pituitary tumours; BioScientifica; Journal of Endocrinology; 245; 2; 5-2020; 179-191
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