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Verfasst von:Rigalli, Juan Pablo [VerfasserIn]   i
 Reichel, Matthias [VerfasserIn]   i
 Reuter, Tasmin [VerfasserIn]   i
 Tocchetti, Guillermo Nicolás [VerfasserIn]   i
 Dyckhoff, Gerhard [VerfasserIn]   i
 Herold-Mende, Christel [VerfasserIn]   i
 Theile, Dirk [VerfasserIn]   i
 Weiß, Johanna [VerfasserIn]   i
Titel:The pregnane X receptor (PXR) and the nuclear receptor corepressor 2 (NCoR2) modulate cell growth in head and neck squamous cell carcinoma
Verf.angabe:Juan Pablo Rigalli, Matthias Reichel, Tasmin Reuter, Guillermo Nicolás Tocchetti, Gerhard Dyckhoff, Christel Herold-Mende, Dirk Theile, Johanna Weiss
E-Jahr:2018
Jahr:February 22, 2018
Umfang:17 S.
Fussnoten:Gesehen am 19.07.2018
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2018
Band/Heft Quelle:13(2018,2) Artikel-Nummer e0193242, 17 Seiten
ISSN Quelle:1932-6203
Abstract:Head 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.
DOI:doi:10.1371/journal.pone.0193242
URL:kostenfrei: Volltext ; Verlag: http://dx.doi.org/10.1371/journal.pone.0193242
 kostenfrei: Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193242
 DOI: https://doi.org/10.1371/journal.pone.0193242
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Apoptosis
 Cell growth
 Cofactors (biochemistry)
 Crystal violet staining
 Gene expression
 Head and neck squamous cell carcinoma
 Plasmid construction
 Prognosis
K10plus-PPN:1577757068
Verknüpfungen:→ Zeitschrift
 
 
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