Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2475-2482
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2475
Estrogen receptors in gastric cancer: Advances and perspectives
Muhammad Saif Ur Rahman, Jiang Cao
Muhammad Saif Ur Rahman, Jiang Cao, Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Author contributions: Rahman MS and Cao J wrote the paper.
Supported by The National Natural Science Foundation of China, No. 30271450, No. 30471955, No. 30672365 and No. 81172516.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jiang Cao, PhD, Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China. caoj@zju.edu.cn
Telephone: +86-571-87315202 Fax: +86-571-87315201
Received: September 30, 2015
Peer-review started: October 1, 2015
First decision: November 5, 2015
Revised: November 23, 2015
Accepted: December 12, 2015
Article in press: December 14, 2015
Published online: February 28, 2016
Abstract

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.

Keywords: Gastric cancer, Estrogen receptor, Isoform, Carcinogenesis, Mechanism, Genomic pathway, Non-genomic pathway

Core tip: Gastric cancer is one of the common malignancies worldwide with high mortality. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes of different tissues. Dysregulation of ERs is associated with many diseases, including gastric cancer. Studies have been conducted to investigate the roles that ERs play in gastric cancer and the clinical relevance of deregulated ERs in gastric cancer patients. This review focuses on the current understanding of ERs in gastric cancer and proposes directions for future investigations.