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ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway
BACKGROUND: Acquired tamoxifen resistance is one of the major barriers to the successful treatment of breast cancer. Recently, overexpression of ERα36 was demonstrated to be a potential mechanism for the generation of acquired tamoxifen resistance. This study aims to evaluate the possibility of ERα3...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969677/ https://www.ncbi.nlm.nih.gov/pubmed/32021441 http://dx.doi.org/10.2147/CMAR.S226410 |
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author | Li, Guangliang Zhang, Jing Xu, Zhenzhen Li, Zhongqi |
author_facet | Li, Guangliang Zhang, Jing Xu, Zhenzhen Li, Zhongqi |
author_sort | Li, Guangliang |
collection | PubMed |
description | BACKGROUND: Acquired tamoxifen resistance is one of the major barriers to the successful treatment of breast cancer. Recently, overexpression of ERα36 was demonstrated to be a potential mechanism for the generation of acquired tamoxifen resistance. This study aims to evaluate the possibility of ERα36 being a therapeutic target for tamoxifen-resistant breast cancer. METHODS: A tamoxifen-resistant cell subline (MCF-7/TAM) was established by culturing MCF-7 cells in medium plus 1 μM tamoxifen over 6 months. Colony-forming assay was used to determine the sensitivity of MCF-7/TAM cells to tamoxifen. Stable transfection was used to knockdown ERα36 expression in MCF-7/TAM cells. MTT assay and Transwell migration assay were used to assess the in vitro proliferation and migration, respectively. Nude mouse tumorigenicity assay was used to evaluate in vivo tumorigenicity. Western blot analysis and quantitative real-time PCR (qRT-PCR) were used to examine the expression of ERα36, ERα, EGFR and phosphorylated ERK1/2. The dual-luciferase reporter assay was used to determine the effect of ERα36 on the activity of EGFR-promotor. RESULTS: MCF-7/TAM cells possessed greatly increased ERα36 expression and EGFR expression and exhibited significantly increased in vitro proliferation and migration ability, as well as increased in vivo tumor growth ability, compared to parental MCF-7 cells. Knockdown of ERα36 expression inhibited in vitro proliferation and migration, as well as in vivo tumor growth ability of MCF-7/TAM cells. ERα36 regulated EGFR expression at the transcriptional level, and knockdown of ERα36 in MCF-7/TAM cells downregulated EGFR expression and then blocked EGFR/ERK signaling pathway. CONCLUSION: Knockdown of ERα36 inhibits the growth of MCF-7/TAM cells in vitro and in vivo by blocking EGFR/ERK signaling pathway. ERα36 may be a candidate therapeutic target for the treatment of tamoxifen-resistant breast cancer. |
format | Online Article Text |
id | pubmed-6969677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-69696772020-02-04 ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway Li, Guangliang Zhang, Jing Xu, Zhenzhen Li, Zhongqi Cancer Manag Res Original Research BACKGROUND: Acquired tamoxifen resistance is one of the major barriers to the successful treatment of breast cancer. Recently, overexpression of ERα36 was demonstrated to be a potential mechanism for the generation of acquired tamoxifen resistance. This study aims to evaluate the possibility of ERα36 being a therapeutic target for tamoxifen-resistant breast cancer. METHODS: A tamoxifen-resistant cell subline (MCF-7/TAM) was established by culturing MCF-7 cells in medium plus 1 μM tamoxifen over 6 months. Colony-forming assay was used to determine the sensitivity of MCF-7/TAM cells to tamoxifen. Stable transfection was used to knockdown ERα36 expression in MCF-7/TAM cells. MTT assay and Transwell migration assay were used to assess the in vitro proliferation and migration, respectively. Nude mouse tumorigenicity assay was used to evaluate in vivo tumorigenicity. Western blot analysis and quantitative real-time PCR (qRT-PCR) were used to examine the expression of ERα36, ERα, EGFR and phosphorylated ERK1/2. The dual-luciferase reporter assay was used to determine the effect of ERα36 on the activity of EGFR-promotor. RESULTS: MCF-7/TAM cells possessed greatly increased ERα36 expression and EGFR expression and exhibited significantly increased in vitro proliferation and migration ability, as well as increased in vivo tumor growth ability, compared to parental MCF-7 cells. Knockdown of ERα36 expression inhibited in vitro proliferation and migration, as well as in vivo tumor growth ability of MCF-7/TAM cells. ERα36 regulated EGFR expression at the transcriptional level, and knockdown of ERα36 in MCF-7/TAM cells downregulated EGFR expression and then blocked EGFR/ERK signaling pathway. CONCLUSION: Knockdown of ERα36 inhibits the growth of MCF-7/TAM cells in vitro and in vivo by blocking EGFR/ERK signaling pathway. ERα36 may be a candidate therapeutic target for the treatment of tamoxifen-resistant breast cancer. Dove 2020-01-14 /pmc/articles/PMC6969677/ /pubmed/32021441 http://dx.doi.org/10.2147/CMAR.S226410 Text en © 2020 Li et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Li, Guangliang Zhang, Jing Xu, Zhenzhen Li, Zhongqi ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway |
title | ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway |
title_full | ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway |
title_fullStr | ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway |
title_full_unstemmed | ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway |
title_short | ERα36 as a Potential Therapeutic Target for Tamoxifen-Resistant Breast Cancer Cell Line Through EGFR/ERK Signaling Pathway |
title_sort | erα36 as a potential therapeutic target for tamoxifen-resistant breast cancer cell line through egfr/erk signaling pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969677/ https://www.ncbi.nlm.nih.gov/pubmed/32021441 http://dx.doi.org/10.2147/CMAR.S226410 |
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