| Title: |
Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer |
| Authors: |
Leonardi, Daiana Beatriz; Anselmino, Nicolás; Brandani, Javier Nahuel; Jaworski, Felipe Martín; Paez, Alejandra; Mazaira, Gisela Ileana; Meiss, Roberto P.; Nuñez, Myriam; Nemirovsky, Sergio Ivan; Giudice, Jimena; Galigniana, Mario Daniel; Pecci, Adali; Gueron, Geraldine; Vazquez, Elba Susana; Cotignola, Javier Hernan |
| Publisher Information: |
Molecular Diversity Preservation International |
| Collection: |
CONICET Digital (Consejo Nacional de Investigaciones Científicas y Técnicas) |
| Subject Terms: |
GLUCOCORTICOID RECEPTOR; HEME OXYGENASE 1; PROSTATE CANCER; https://purl.org/becyt/ford/3.1; https://purl.org/becyt/ford/3 |
| Description: |
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. ; Fil: Leonardi, Daiana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina ; Fil: Anselmino, Nicolás. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1422-0067/20/5/1006; https://hdl.handle.net/11336/103547; CONICET Digital; CONICET |
| Availability: |
https://hdl.handle.net/11336/103547 |
| Rights: |
info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/2.5/ar/ |
| Accession Number: |
edsbas.E3E2B137 |
| Database: |
BASE |