dc.creatorRigalli, Juan Pablo
dc.creatorReichel, Matthias
dc.creatorReuter, Tasmin
dc.creatorTocchetti, Guillermo Nicolás
dc.creatorDyckhoff, Gerhard
dc.creatorHerold Mende, Christel
dc.creatorTheile, Dirk
dc.creatorWeiss, Johanna
dc.date.accessioned2019-10-23T21:12:52Z
dc.date.accessioned2022-10-15T02:53:24Z
dc.date.available2019-10-23T21:12:52Z
dc.date.available2022-10-15T02:53:24Z
dc.date.created2019-10-23T21:12:52Z
dc.date.issued2018-02
dc.identifierRigalli, Juan Pablo; Reichel, Matthias; Reuter, Tasmin; Tocchetti, Guillermo Nicolás; Dyckhoff, Gerhard; et al.; The pregnane X receptor (PXR) and the nuclear receptor corepressor 2 (NCoR2) modulate cell growth in head and neck squamous cell carcinoma; Public Library of Science; Plos One; 13; 2; 2-2018; 1-17; e0193242
dc.identifier1932-6203
dc.identifierhttp://hdl.handle.net/11336/87185
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4337218
dc.description.abstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide. The pregnane X receptor (PXR) is a nuclear receptor regulating several target genes associated with cancer malignancy. We here demonstrated a significant effect of PXR on HNSCC cell growth, as evidenced in PXR knock-down experiments. PXR transcriptional activity is more importantly regulated by the presence of coactivators and corepressors than by PXR protein expression. To date, there is scarce information on the regulation of PXR in HNSCC and on its role in the pathogenesis of this disease. Coactivator and corepressor expression was screened through qRT-PCR in 8 HNSCC cell lines and correlated to PXR activity, determined by using a reporter gene assay. All cell lines considerably expressed all the cofactors assessed. PXR activity negatively correlated with nuclear receptor corepressor 2 (NCoR2) expression, indicating a major role of this corepressor in PXR modulation and suggesting its potential as a surrogate for PXR activity in HNSCC. To test the association of NCoR2 with the malignant phenotype, a subset of three cell lines was transfected with an over-expression plasmid for this corepressor. Subsequently, cell growth and chemoresistance assays were performed. To elucidate the mechanisms underlying NCoR2 effects on cell growth, caspase 3/7 activity and protein levels of cleaved caspase 3 and PARP were evaluated. In HNO97 cells, NCoR2 over-expression decreased cell growth, chemoresistance and increased cleaved caspase 3 levels, caspase activity and cleaved PARP levels. On the contrary, in HNO124 and HNO210 cells, NCoR2 over-expression increased cell growth, drug resistance and decreased cleaved caspase 3 levels, caspase activity and cleaved PARP levels. In conclusion, we demonstrated a role of PXR and NCoR2 in the modulation of cell growth in HNSCC. This may contribute to a better understanding of the highly variable HNSCC therapeutic response.
dc.languageeng
dc.publisherPublic Library of Science
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0193242
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193242
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectPXR
dc.subjectHNSCC
dc.subjectNCOR2
dc.subjectNUCLEAR RECEPTORS
dc.titleThe pregnane X receptor (PXR) and the nuclear receptor corepressor 2 (NCoR2) modulate cell growth in head and neck squamous cell carcinoma
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


Este ítem pertenece a la siguiente institución