Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/112027
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Type: Journal article
Title: Androgen signaling in esophageal adenocarcinoma cell lines in vitro
Author: Palethorpe, H.
Drew, P.
Smith, E.
Citation: Digestive Diseases and Sciences, 2017; 62(12):3402-3414
Publisher: Springer
Issue Date: 2017
ISSN: 0163-2116
1573-2568
Statement of
Responsibility: 
Helen M. Palethorpe, Paul A. Drew, Eric Smith
Abstract: Background: We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer. Aim: To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro. Methods and Results: In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation. Conclusions: This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC.
Keywords: Esophageal adenocarcinoma, androgen receptor, fibroblast, FKBP, dihydrotestosterone, direct co-culture, in vitro
Rights: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
RMID: 0030076887
DOI: 10.1007/s10620-017-4794-5
Appears in Collections:Medicine publications

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