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Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression

Cervical adenocarcinomas are believed to lose estrogen response on the basis of no expression of a nuclear estrogen receptor such as ERα in clinical pathology. Here, we demonstrated that cervical adenocarcinoma cells respond to a physiological concentration of estrogen to upregulate claudin-1, a cel...

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Autores principales: Akimoto, Taishi, Takasawa, Akira, Takasawa, Kumi, Aoyama, Tomoyuki, Murata, Masaki, Osanai, Makoto, Saito, Tsuyoshi, Sawada, Norimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141703/
https://www.ncbi.nlm.nih.gov/pubmed/30227306
http://dx.doi.org/10.1016/j.neo.2018.08.010
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author Akimoto, Taishi
Takasawa, Akira
Takasawa, Kumi
Aoyama, Tomoyuki
Murata, Masaki
Osanai, Makoto
Saito, Tsuyoshi
Sawada, Norimasa
author_facet Akimoto, Taishi
Takasawa, Akira
Takasawa, Kumi
Aoyama, Tomoyuki
Murata, Masaki
Osanai, Makoto
Saito, Tsuyoshi
Sawada, Norimasa
author_sort Akimoto, Taishi
collection PubMed
description Cervical adenocarcinomas are believed to lose estrogen response on the basis of no expression of a nuclear estrogen receptor such as ERα in clinical pathology. Here, we demonstrated that cervical adenocarcinoma cells respond to a physiological concentration of estrogen to upregulate claudin-1, a cell surface molecule highly expressed in cervical adenocarcinomas. Knockout of claudin-1 induced apoptosis and significantly inhibited proliferation, migration, and invasion of cervical adenocarcinoma cells and tumorigenicity in vivo. Importantly, all of the cervical adenocarcinoma cell lines examined expressed a membrane-bound type estrogen receptor, G protein–coupled receptor 30 (GPR30/GPER1), but not ERα. Estrogen-dependent induction of claudin-1 expression was mediated by GPR30 via ERK and/or Akt signaling. In surgical specimens, there was a positive correlation between claudin-1 expression and GPR30 expression. Double high expression of claudin-1 and GPR30 predicts poor prognosis in patients with cervical adenocarcinomas. Mechanism-based targeting of estrogen/GPR30 signaling and claudin-1 may be effective for cervical adenocarcinoma therapy.
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spelling pubmed-61417032018-09-20 Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression Akimoto, Taishi Takasawa, Akira Takasawa, Kumi Aoyama, Tomoyuki Murata, Masaki Osanai, Makoto Saito, Tsuyoshi Sawada, Norimasa Neoplasia Original article Cervical adenocarcinomas are believed to lose estrogen response on the basis of no expression of a nuclear estrogen receptor such as ERα in clinical pathology. Here, we demonstrated that cervical adenocarcinoma cells respond to a physiological concentration of estrogen to upregulate claudin-1, a cell surface molecule highly expressed in cervical adenocarcinomas. Knockout of claudin-1 induced apoptosis and significantly inhibited proliferation, migration, and invasion of cervical adenocarcinoma cells and tumorigenicity in vivo. Importantly, all of the cervical adenocarcinoma cell lines examined expressed a membrane-bound type estrogen receptor, G protein–coupled receptor 30 (GPR30/GPER1), but not ERα. Estrogen-dependent induction of claudin-1 expression was mediated by GPR30 via ERK and/or Akt signaling. In surgical specimens, there was a positive correlation between claudin-1 expression and GPR30 expression. Double high expression of claudin-1 and GPR30 predicts poor prognosis in patients with cervical adenocarcinomas. Mechanism-based targeting of estrogen/GPR30 signaling and claudin-1 may be effective for cervical adenocarcinoma therapy. Neoplasia Press 2018-09-15 /pmc/articles/PMC6141703/ /pubmed/30227306 http://dx.doi.org/10.1016/j.neo.2018.08.010 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Akimoto, Taishi
Takasawa, Akira
Takasawa, Kumi
Aoyama, Tomoyuki
Murata, Masaki
Osanai, Makoto
Saito, Tsuyoshi
Sawada, Norimasa
Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
title Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
title_full Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
title_fullStr Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
title_full_unstemmed Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
title_short Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
title_sort estrogen/gpr30 signaling contributes to the malignant potentials of er-negative cervical adenocarcinoma via regulation of claudin-1 expression
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141703/
https://www.ncbi.nlm.nih.gov/pubmed/30227306
http://dx.doi.org/10.1016/j.neo.2018.08.010
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