info:eu-repo/semantics/article
Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer
Fecha
2019-02Registro en:
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
1449-2288
1422-0067
CONICET Digital
CONICET
Autor
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
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.