The down regulations of HSD11B1 and NR3C1 in primary and metastatic PC may diminish the anti-inflammation and anti-proliferation effects of glucocorticoids signaling.
<sup>18</sup>F-GR02 also accumulated in GR positive subcutaneous and subrenal capsule prostate cancer models, and uptake in tumors was competed by mifepristone.
Importantly, GR inhibition by RNAi or chemical blockade results in impaired proliferation and 3D-spheroid formation in all tested cell lines.<b>Conclusions:</b> GR upregulation seems to be a common mechanism during antiandrogen treatment and supports the notion that targeting the GR pathway combined with antiandrogen medication may further improve prostate cancer therapy.<i></i>.
Furthermore, GR-regulated proliferation-associated genes <i>AKAP12, FKBP5, SGK1, CEBPD</i>, and <i>ZBTB16</i> are inhibited by CORT108297 treatment <i>in vivo</i> Together, these data suggest that GR-selective nonsteroidal SGRMs potently inhibit GR activity and prostate cancer growth despite AR pathway inhibition, demonstrating the therapeutic potential of SGRMs in GR-expressing CRPC.<i></i>.
We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance.
The GR and the AR are central regulators of various metabolic, homeostatic and differentiation processes and hence important therapeutic targets, especially in inflammation and prostate cancer, respectively.
This shift in cancer cell redox homeostasis by ES significantly decreased the effect of protumorigenic oxidative machinery on androgen-independent PCa growth, suggesting that ES can suppress GR-induced resistant phenotype upon AR antagonism and that the dual targeting action of ES on AR and GR can be further translated to PCa therapy.-Lee, J. H., Kang, M., Wang, H., Naik, G., Mobley, J.
Inhibition of the glucocorticoid receptor results in an enhanced miR-99a/100-mediated radiation response in stem-like cells from human prostate cancers.
Enrichment analysis indicated that genomic regions in the following 15 categories were enriched for the PCa risk-associated SNPs: exons, CpG regions, 6 TFs (AR, ERG, FOXA1, HOXB13, CTCF, and NR3C1), 5 HMs (H3K4me1, H3K4me2, H3K4me3, H3K27AC, and H3T11P), DHSs and POLR2A.
We studied CWR-22Rv1 and LAPC4 AR/GR-expressing PC cell lines following treatment with combinations of the androgen R1881, AR antagonist MDV3100, GR agonist dexamethasone, GR antagonists mifepristone and CORT 122928, or the SGK1 inhibitor GSK650394.
These data suggested that TGFbeta1, uPA, and IGF-I mediate at least in part cell-cell interactions and GR function in PA-III prostate cancer and UMR 106 osteosarcoma cells.