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PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB

Prostate-specific G-protein-coupled receptor (PSGR), a member of the olfactory subfamily of G-protein-coupled receptors, is specifically expressed in human prostate tissue and overexpressed in prostate cancer (PCa). This expression pattern suggests a possible role in PCa initiation and progression....

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Autores principales: Rodriguez, M, Luo, W, Weng, J, Zeng, L, Yi, Z, Siwko, S, Liu, M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189964/
https://www.ncbi.nlm.nih.gov/pubmed/25111863
http://dx.doi.org/10.1038/oncsis.2014.29
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author Rodriguez, M
Luo, W
Weng, J
Zeng, L
Yi, Z
Siwko, S
Liu, M
author_facet Rodriguez, M
Luo, W
Weng, J
Zeng, L
Yi, Z
Siwko, S
Liu, M
author_sort Rodriguez, M
collection PubMed
description Prostate-specific G-protein-coupled receptor (PSGR), a member of the olfactory subfamily of G-protein-coupled receptors, is specifically expressed in human prostate tissue and overexpressed in prostate cancer (PCa). This expression pattern suggests a possible role in PCa initiation and progression. We developed a PSGR transgenic mouse model driven by a probasin promoter and investigated the role of PSGR in prostate malignancy. Overexpression of PSGR induced a chronic inflammatory response that ultimately gave rise to premalignant mouse prostate intraepithelial neoplasia lesions in later stages of life. PSGR-overexpressing LnCaP cells in prostate xenografts formed larger tumors compared with normal LnCaP cancer cells, suggesting a role of PSGR in the promotion of tumor development. Furthermore, we identified nuclear factor-κB (NF-κB) or RELA as a key downstream target activated by PSGR signaling. We also show that this regulation was mediated in part by the phosphatidylinositol-3-kinase/Akt (PI3K/AKT) pathway, highlighting a collaborative role between PI3K/AKT and NF-κB during tumor inflammation downstream of PSGR in the initial phases of prostate disease.
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spelling pubmed-51899642017-01-13 PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB Rodriguez, M Luo, W Weng, J Zeng, L Yi, Z Siwko, S Liu, M Oncogenesis Original Article Prostate-specific G-protein-coupled receptor (PSGR), a member of the olfactory subfamily of G-protein-coupled receptors, is specifically expressed in human prostate tissue and overexpressed in prostate cancer (PCa). This expression pattern suggests a possible role in PCa initiation and progression. We developed a PSGR transgenic mouse model driven by a probasin promoter and investigated the role of PSGR in prostate malignancy. Overexpression of PSGR induced a chronic inflammatory response that ultimately gave rise to premalignant mouse prostate intraepithelial neoplasia lesions in later stages of life. PSGR-overexpressing LnCaP cells in prostate xenografts formed larger tumors compared with normal LnCaP cancer cells, suggesting a role of PSGR in the promotion of tumor development. Furthermore, we identified nuclear factor-κB (NF-κB) or RELA as a key downstream target activated by PSGR signaling. We also show that this regulation was mediated in part by the phosphatidylinositol-3-kinase/Akt (PI3K/AKT) pathway, highlighting a collaborative role between PI3K/AKT and NF-κB during tumor inflammation downstream of PSGR in the initial phases of prostate disease. Nature Publishing Group 2014-08 2014-08-11 /pmc/articles/PMC5189964/ /pubmed/25111863 http://dx.doi.org/10.1038/oncsis.2014.29 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Rodriguez, M
Luo, W
Weng, J
Zeng, L
Yi, Z
Siwko, S
Liu, M
PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB
title PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB
title_full PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB
title_fullStr PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB
title_full_unstemmed PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB
title_short PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB
title_sort psgr promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through nf-κb
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189964/
https://www.ncbi.nlm.nih.gov/pubmed/25111863
http://dx.doi.org/10.1038/oncsis.2014.29
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