Cargando…

Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer

Prostate cancer (PCa) treatment was first established by Huggins and Hodges in 1941, primarily described as androgen deprivation via interference of testicular androgen production. The disease remains incurable with relapse of hormone-refractory cancer after treatments. Epidemiological and clinical...

Descripción completa

Detalles Bibliográficos
Autores principales: Lau, Kin-Mang, To, Ka-Fai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037713/
https://www.ncbi.nlm.nih.gov/pubmed/27589731
http://dx.doi.org/10.3390/ijms17091434
_version_ 1782455797216706560
author Lau, Kin-Mang
To, Ka-Fai
author_facet Lau, Kin-Mang
To, Ka-Fai
author_sort Lau, Kin-Mang
collection PubMed
description Prostate cancer (PCa) treatment was first established by Huggins and Hodges in 1941, primarily described as androgen deprivation via interference of testicular androgen production. The disease remains incurable with relapse of hormone-refractory cancer after treatments. Epidemiological and clinical studies disclosed the importance of estrogens in PCa. Discovery of estrogen receptor ERβ prompted direct estrogenic actions, in conjunction with ERα, on PCa cells. Mechanistically, ERs upon ligand binding transactivate target genes at consensus genomic sites via interactions with various transcriptional co-regulators to mold estrogenic signaling. With animal models, Noble revealed estrogen dependencies of PCa, providing insight into potential uses of antiestrogens in the treatment. Subsequently, various clinical trials were conducted and molecular and functional consequences of antiestrogen treatment in PCa were delineated. Besides, estrogens can also trigger rapid non-genomic signaling responses initiated at the plasma membrane, at least partially via an orphan G-protein-coupled receptor GPR30. Activation of GPR30 significantly inhibited in vitro and in vivo PCa cell growth and the underlying mechanism was elucidated. Currently, molecular networks of estrogenic and antiestrogenic signaling via ERα, ERβ and GPR30 in PCa have not been fully deciphered. This crucial information could be beneficial to further developments of effective estrogen- and antiestrogen-based therapy for PCa patients.
format Online
Article
Text
id pubmed-5037713
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-50377132016-09-29 Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer Lau, Kin-Mang To, Ka-Fai Int J Mol Sci Review Prostate cancer (PCa) treatment was first established by Huggins and Hodges in 1941, primarily described as androgen deprivation via interference of testicular androgen production. The disease remains incurable with relapse of hormone-refractory cancer after treatments. Epidemiological and clinical studies disclosed the importance of estrogens in PCa. Discovery of estrogen receptor ERβ prompted direct estrogenic actions, in conjunction with ERα, on PCa cells. Mechanistically, ERs upon ligand binding transactivate target genes at consensus genomic sites via interactions with various transcriptional co-regulators to mold estrogenic signaling. With animal models, Noble revealed estrogen dependencies of PCa, providing insight into potential uses of antiestrogens in the treatment. Subsequently, various clinical trials were conducted and molecular and functional consequences of antiestrogen treatment in PCa were delineated. Besides, estrogens can also trigger rapid non-genomic signaling responses initiated at the plasma membrane, at least partially via an orphan G-protein-coupled receptor GPR30. Activation of GPR30 significantly inhibited in vitro and in vivo PCa cell growth and the underlying mechanism was elucidated. Currently, molecular networks of estrogenic and antiestrogenic signaling via ERα, ERβ and GPR30 in PCa have not been fully deciphered. This crucial information could be beneficial to further developments of effective estrogen- and antiestrogen-based therapy for PCa patients. MDPI 2016-08-31 /pmc/articles/PMC5037713/ /pubmed/27589731 http://dx.doi.org/10.3390/ijms17091434 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lau, Kin-Mang
To, Ka-Fai
Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer
title Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer
title_full Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer
title_fullStr Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer
title_full_unstemmed Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer
title_short Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer
title_sort importance of estrogenic signaling and its mediated receptors in prostate cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037713/
https://www.ncbi.nlm.nih.gov/pubmed/27589731
http://dx.doi.org/10.3390/ijms17091434
work_keys_str_mv AT laukinmang importanceofestrogenicsignalinganditsmediatedreceptorsinprostatecancer
AT tokafai importanceofestrogenicsignalinganditsmediatedreceptorsinprostatecancer