Cargando…

Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors

Background: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonab...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Fung-Wei, Fan, Hueng-Chuen, Liu, Jui-Ming, Fan, Tai-Ping, Jing, Jin, Yang, Chia-Ling, Hsu, Ren-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297796/
https://www.ncbi.nlm.nih.gov/pubmed/28098816
http://dx.doi.org/10.3390/ijms18010163
_version_ 1782505784900321280
author Chang, Fung-Wei
Fan, Hueng-Chuen
Liu, Jui-Ming
Fan, Tai-Ping
Jing, Jin
Yang, Chia-Ling
Hsu, Ren-Jun
author_facet Chang, Fung-Wei
Fan, Hueng-Chuen
Liu, Jui-Ming
Fan, Tai-Ping
Jing, Jin
Yang, Chia-Ling
Hsu, Ren-Jun
author_sort Chang, Fung-Wei
collection PubMed
description Background: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. Results: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line. Therefore, we believe that these three genes increase the tolerance of MCF7 to mitoxantrone (MX). The data showed that the high expression of COX6C made MCF-7/MX have more stable on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) expression than normal MCF7 cells under hypoxic conditions. The accumulation of MX was greater in the ATP-depleted treatment MCF7/MX cells than in normal MCF7/MX cells. Furthermore, E2 increased the tolerance of MCF7 cells to MX through inducing the expression of ABCG2. However, E2 could not increase the expression of ABCG2 after the inhibition of estrogen receptor α (ERα) in MCF7 cells. According to the above data, under the E2 treatment, MDA-MB231, which lacks ER, had a higher sensitivity to MX than MCF7 cells. Conclusions: E2 induced the expression of ABCG2 through ERα and the over-expressed ABCG2 made MCF7 more tolerant to MX. Moreover, the over-expressed ATP synthase and COX6c affected mitochondrial genes and function causing the over-expressed ABCG2 cells pumped out MX in a concentration gradient from the cell matrix. Finally lead to chemoresistance.
format Online
Article
Text
id pubmed-5297796
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-52977962017-02-10 Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors Chang, Fung-Wei Fan, Hueng-Chuen Liu, Jui-Ming Fan, Tai-Ping Jing, Jin Yang, Chia-Ling Hsu, Ren-Jun Int J Mol Sci Article Background: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. Results: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line. Therefore, we believe that these three genes increase the tolerance of MCF7 to mitoxantrone (MX). The data showed that the high expression of COX6C made MCF-7/MX have more stable on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) expression than normal MCF7 cells under hypoxic conditions. The accumulation of MX was greater in the ATP-depleted treatment MCF7/MX cells than in normal MCF7/MX cells. Furthermore, E2 increased the tolerance of MCF7 cells to MX through inducing the expression of ABCG2. However, E2 could not increase the expression of ABCG2 after the inhibition of estrogen receptor α (ERα) in MCF7 cells. According to the above data, under the E2 treatment, MDA-MB231, which lacks ER, had a higher sensitivity to MX than MCF7 cells. Conclusions: E2 induced the expression of ABCG2 through ERα and the over-expressed ABCG2 made MCF7 more tolerant to MX. Moreover, the over-expressed ATP synthase and COX6c affected mitochondrial genes and function causing the over-expressed ABCG2 cells pumped out MX in a concentration gradient from the cell matrix. Finally lead to chemoresistance. MDPI 2017-01-14 /pmc/articles/PMC5297796/ /pubmed/28098816 http://dx.doi.org/10.3390/ijms18010163 Text en © 2017 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 Article
Chang, Fung-Wei
Fan, Hueng-Chuen
Liu, Jui-Ming
Fan, Tai-Ping
Jing, Jin
Yang, Chia-Ling
Hsu, Ren-Jun
Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors
title Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors
title_full Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors
title_fullStr Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors
title_full_unstemmed Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors
title_short Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors
title_sort estrogen enhances the expression of the multidrug transporter gene abcg2—increasing drug resistance of breast cancer cells through estrogen receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297796/
https://www.ncbi.nlm.nih.gov/pubmed/28098816
http://dx.doi.org/10.3390/ijms18010163
work_keys_str_mv AT changfungwei estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors
AT fanhuengchuen estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors
AT liujuiming estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors
AT fantaiping estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors
AT jingjin estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors
AT yangchialing estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors
AT hsurenjun estrogenenhancestheexpressionofthemultidrugtransportergeneabcg2increasingdrugresistanceofbreastcancercellsthroughestrogenreceptors