dc.creator | Mongi Bragato, Bethania del Carmen | |
dc.creator | Grondona, Ezequiel | |
dc.creator | Sosa, Liliana del Valle | |
dc.creator | Zlocowski, Natacha | |
dc.creator | Venier, Ana Clara | |
dc.creator | Torres, Alicia Ines | |
dc.creator | Latini, Alexandra | |
dc.creator | Bainy Leal, Rodrigo | |
dc.creator | Gutiérrez, Silvina | |
dc.creator | de Paul, Ana Lucia | |
dc.date.accessioned | 2021-09-16T14:19:54Z | |
dc.date.accessioned | 2022-10-15T03:50:56Z | |
dc.date.available | 2021-09-16T14:19:54Z | |
dc.date.available | 2022-10-15T03:50:56Z | |
dc.date.created | 2021-09-16T14:19:54Z | |
dc.date.issued | 2020-05 | |
dc.identifier | 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 | |
dc.identifier | 0022-0795 | |
dc.identifier | http://hdl.handle.net/11336/140524 | |
dc.identifier | 1479-6805 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4342122 | |
dc.description.abstract | 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. | |
dc.language | eng | |
dc.publisher | BioScientifica | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1530/JOE-19-0506 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://joe.bioscientifica.com/view/journals/joe/245/2/JOE-19-0506.xml | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | NF-ΚB | |
dc.subject | PITUITARY TUMOUR | |
dc.subject | PROLIFERATION | |
dc.subject | SA-B-GAL | |
dc.subject | SENESCENCE | |
dc.title | Pivotal role of NF-κB in cellular senescence of experimental pituitary tumours | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |