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Article

Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer

1
Laboratorio de Inflamación y Cáncer, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina
2
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina
3
Laboratorio de Biología Celular y Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina
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Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina
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Departamento de Físico-Matemática, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Cátedra de Matemática, Buenos Aires C1113AAD, Argentina
6
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina
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Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599-7545, USA
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McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599-7126, USA
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Laboratorio de Receptores Nucleares, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires C1428ADN, Argentina
10
Biología Molecular y Neurociencias (IFIBYNE), Instituto de Fisiología, CONICET—Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1006; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051006
Received: 30 January 2019 / Revised: 18 February 2019 / Accepted: 21 February 2019 / Published: 26 February 2019
(This article belongs to the Special Issue Protective and Detrimental Role of Heme Oxygenase-1)
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. View Full-Text
Keywords: glucocorticoid receptor; GR; heme oxygenase 1; HO-1; prostate cancer glucocorticoid receptor; GR; heme oxygenase 1; HO-1; prostate cancer
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MDPI and ACS Style

Leonardi, D.B.; Anselmino, N.; Brandani, J.N.; Jaworski, F.M.; Páez, A.V.; Mazaira, G.; Meiss, R.P.; Nuñez, M.; Nemirovsky, S.I.; Giudice, J.; Galigniana, M.; Pecci, A.; Gueron, G.; Vazquez, E.; Cotignola, J. Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer. Int. J. Mol. Sci. 2019, 20, 1006. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051006

AMA Style

Leonardi DB, Anselmino N, Brandani JN, Jaworski FM, Páez AV, Mazaira G, Meiss RP, Nuñez M, Nemirovsky SI, Giudice J, Galigniana M, Pecci A, Gueron G, Vazquez E, Cotignola J. Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer. International Journal of Molecular Sciences. 2019; 20(5):1006. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051006

Chicago/Turabian Style

Leonardi, Daiana B., Nicolás Anselmino, Javier N. Brandani, Felipe M. Jaworski, Alejandra V. Páez, Gisela Mazaira, Roberto P. Meiss, Myriam Nuñez, Sergio I. Nemirovsky, Jimena Giudice, Mario Galigniana, Adalí Pecci, Geraldine Gueron, Elba Vazquez, and Javier Cotignola. 2019. "Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer" International Journal of Molecular Sciences 20, no. 5: 1006. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051006

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