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Artículo

Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer

Leonardi, Daiana BeatrizIcon ; Anselmino, NicolásIcon ; Brandani, Javier NahuelIcon ; Jaworski, Felipe MartínIcon ; Paez, AlejandraIcon ; Mazaira, Gisela IleanaIcon ; Meiss, Roberto P.; Nuñez, Myriam; Nemirovsky, Sergio IvanIcon ; Giudice, JimenaIcon ; Galigniana, Mario DanielIcon ; Pecci, AdaliIcon ; Gueron, GeraldineIcon ; Vazquez, Elba SusanaIcon ; Cotignola, Javier HernanIcon
Fecha de publicación: 02/2019
Editorial: Molecular Diversity Preservation International
Revista: International Journal of Molecular Sciences
ISSN: 1449-2288
e-ISSN: 1422-0067
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Glucocorticoids are used during prostate cancer (PCa) treatment. However, they may also have the potential to drive castration resistant prostate cancer (CRPC) growth via the glucocorticoid receptor (GR). Given the association between inflammation and PCa, and the anti-inflammatory role of heme oxygenase 1 (HO-1), we aimed at identifying the molecular processes governed by the interaction between HO-1 and GR. PCa-derived cell lines were treated with Hemin, Dexamethasone (Dex), or both. We studied GR gene expression by RTqPCR, protein expression by Western Blot, transcriptional activity using reporter assays, and nuclear translocation by confocal microscopy. We also evaluated the expression of HO-1, FKBP51, and FKBP52 by Western Blot. Hemin pre-treatment reduced Dex-induced GR activity in PC3 cells. Protein levels of FKBP51, a cytoplasmic GR-binding immunophilin, were significantly increased in Hemin+Dex treated cells, possibly accounting for lower GR activity. We also evaluated these treatments in vivo using PC3 tumors growing as xenografts. We found non-significant differences in tumor growth among treatments. Immunohistochemistry analyses revealed strong nuclear GR staining in almost all groups. We did not observe HO-1 staining in tumor cells, but high HO-1 reactivity was detected in tumor infiltrating macrophages. Our results suggest an association and crossed modulation between HO-1 and GR pathways.
Palabras clave: GLUCOCORTICOID RECEPTOR , HEME OXYGENASE 1 , PROSTATE CANCER
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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 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/103547
URL: http://www.mdpi.com/1422-0067/20/5/1006
DOI: http://dx.doi.org/10.3390/ijms20051006
Colecciones
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Leonardi, Daiana Beatriz; Anselmino, Nicolás; Brandani, Javier Nahuel; Jaworski, Felipe Martín; Paez, Alejandra; et al.; Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 20; 5; 2-2019
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