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Is the glucocorticoid receptor a key player in prostate cancer?: A literature review

Glucocorticoids act through the glucocorticoid receptor (GR) and exert pleiotropic effects in different cancer types. In prostate cancer cells, GR and androgen receptor (AR) share overlapping transcriptomes and cistromes. Under enzalutamide treatment, GR signaling can bypass AR activation and promot...

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Autores principales: Sakellakis, Minas, Flores, Laura Jacqueline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302310/
https://www.ncbi.nlm.nih.gov/pubmed/35866830
http://dx.doi.org/10.1097/MD.0000000000029716
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author Sakellakis, Minas
Flores, Laura Jacqueline
author_facet Sakellakis, Minas
Flores, Laura Jacqueline
author_sort Sakellakis, Minas
collection PubMed
description Glucocorticoids act through the glucocorticoid receptor (GR) and exert pleiotropic effects in different cancer types. In prostate cancer cells, GR and androgen receptor (AR) share overlapping transcriptomes and cistromes. Under enzalutamide treatment, GR signaling can bypass AR activation and promote castration resistance via the expression of a subset of AR-target genes. However, GR-dependent growth under enhanced antiandrogen inhibition occurs only in a subset of primed cells. On the other hand, glucocorticoids have been used successfully in the treatment of prostate cancer for many years. In the context of AR signaling, GR competes with AR for DNA-binding and has the potential to halt the proliferation rate of prostate cancer cells. Their target genes overlap by <50% and they execute unique functions in vivo. In addition, even when AR and GR upregulate the same transcriptional target gene, the effect might not be identical in magnitude. Besides being able to drive tumor proliferation, GR is also a key player in prostate cancer cell survival. Stimulation of GR activity can undermine the effects of enhanced antiandrogen treatment, chemotherapy and radiotherapy. GR activation in prostate cancer can increase prosurvival gene expression. Identifying the full spectrum of GR activity will inform the optimal use of glucocorticosteroids in prostate cancer. It will also determine the best strategies to target the protumorigenic effects of GR.
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spelling pubmed-93023102022-08-03 Is the glucocorticoid receptor a key player in prostate cancer?: A literature review Sakellakis, Minas Flores, Laura Jacqueline Medicine (Baltimore) Research Article Glucocorticoids act through the glucocorticoid receptor (GR) and exert pleiotropic effects in different cancer types. In prostate cancer cells, GR and androgen receptor (AR) share overlapping transcriptomes and cistromes. Under enzalutamide treatment, GR signaling can bypass AR activation and promote castration resistance via the expression of a subset of AR-target genes. However, GR-dependent growth under enhanced antiandrogen inhibition occurs only in a subset of primed cells. On the other hand, glucocorticoids have been used successfully in the treatment of prostate cancer for many years. In the context of AR signaling, GR competes with AR for DNA-binding and has the potential to halt the proliferation rate of prostate cancer cells. Their target genes overlap by <50% and they execute unique functions in vivo. In addition, even when AR and GR upregulate the same transcriptional target gene, the effect might not be identical in magnitude. Besides being able to drive tumor proliferation, GR is also a key player in prostate cancer cell survival. Stimulation of GR activity can undermine the effects of enhanced antiandrogen treatment, chemotherapy and radiotherapy. GR activation in prostate cancer can increase prosurvival gene expression. Identifying the full spectrum of GR activity will inform the optimal use of glucocorticosteroids in prostate cancer. It will also determine the best strategies to target the protumorigenic effects of GR. Lippincott Williams & Wilkins 2022-07-22 /pmc/articles/PMC9302310/ /pubmed/35866830 http://dx.doi.org/10.1097/MD.0000000000029716 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Sakellakis, Minas
Flores, Laura Jacqueline
Is the glucocorticoid receptor a key player in prostate cancer?: A literature review
title Is the glucocorticoid receptor a key player in prostate cancer?: A literature review
title_full Is the glucocorticoid receptor a key player in prostate cancer?: A literature review
title_fullStr Is the glucocorticoid receptor a key player in prostate cancer?: A literature review
title_full_unstemmed Is the glucocorticoid receptor a key player in prostate cancer?: A literature review
title_short Is the glucocorticoid receptor a key player in prostate cancer?: A literature review
title_sort is the glucocorticoid receptor a key player in prostate cancer?: a literature review
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302310/
https://www.ncbi.nlm.nih.gov/pubmed/35866830
http://dx.doi.org/10.1097/MD.0000000000029716
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