Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer

International Journal of Molecular Sciences
Daiana B LeonardiJavier Cotignola

Abstract

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 staini...Continue Reading

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Citations

Sep 27, 2019·International Journal of Molecular Sciences·Valeria Sorrenti
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Sungyeon ParkJesang Ko
Jan 28, 2021·International Journal of Molecular Sciences·Karolina Bukowska-StrakovaMaciej Siedlar

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Methods Mentioned

BETA
nuclear translocation
co-immunoprecipitation
xenografts
RNAseq
Assay
PCR
Xenograft
light microscopy

Software Mentioned

Ensembl
Mx3000P
Stata
GraphPad Prism
Cistrome
MEME Suit

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