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FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis

BACKGROUND: Tamoxifen is an important choice in endocrine therapy for patients with oestrogen receptor-positive (ER+) breast cancer, and disease progression-associated resistance to tamoxifen therapy is still challenging. Flap endonuclease-1 (FEN1) is used as a prognostic biomarker and is considered...

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Autores principales: Xu, Lu, Shen, Ji-Ming, Qu, Jing-Lei, Song, Na, Che, Xiao-Fang, Hou, Ke-Zuo, Shi, Jing, Zhao, Lei, Shi, Sha, Liu, Yun-Peng, Qu, Xiu-Juan, Teng, Yue-E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940940/
https://www.ncbi.nlm.nih.gov/pubmed/33708885
http://dx.doi.org/10.21037/atm-20-3068
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author Xu, Lu
Shen, Ji-Ming
Qu, Jing-Lei
Song, Na
Che, Xiao-Fang
Hou, Ke-Zuo
Shi, Jing
Zhao, Lei
Shi, Sha
Liu, Yun-Peng
Qu, Xiu-Juan
Teng, Yue-E
author_facet Xu, Lu
Shen, Ji-Ming
Qu, Jing-Lei
Song, Na
Che, Xiao-Fang
Hou, Ke-Zuo
Shi, Jing
Zhao, Lei
Shi, Sha
Liu, Yun-Peng
Qu, Xiu-Juan
Teng, Yue-E
author_sort Xu, Lu
collection PubMed
description BACKGROUND: Tamoxifen is an important choice in endocrine therapy for patients with oestrogen receptor-positive (ER+) breast cancer, and disease progression-associated resistance to tamoxifen therapy is still challenging. Flap endonuclease-1 (FEN1) is used as a prognostic biomarker and is considered to participate in proliferation, migration, and drug resistance in multiple cancers, especially breast cancer, but the prognostic function of FEN1 in ER+ breast cancer, and whether FEN1 is related to tamoxifen resistance or not, remain to be explored. METHODS: On-line database Kaplan-Meier (KM) plotter, GEO datasets, and immunohistochemistry were used to analyse the prognostic value of FEN1 in ER+ breast cancer from mRNA and protein levels. Cell viability assay and colony formation assays showed the response of tamoxifen in MCF-7 and T47D cells. Microarray data with FEN1 siRNA versus control group in MCF-7 cells were analysed by Gene Set Enrichment Analysis (GSEA). The protein levels downstream of FEN1 were detected by western blot assay. RESULTS: ER+ breast cancer patients who received tamoxifen for adjuvant endocrine therapy with poor prognosis showed a high expression of FEN1. MCF-7 and T47D appeared resistant to tamoxifen after FEN1 over-expression and increased sensitivity to tamoxifen after FEN1 knockdown. Importantly, FEN1 over-expression could activate tamoxifen resistance through the ERα/cyclin D1/Rb axis. CONCLUSIONS: As a biomarker of tamoxifen effectiveness, FEN1 participates in tamoxifen resistance through ERα/cyclin D1/Rb axis. In the future, reversing tamoxifen resistance by knocking-down FEN1 or by way of action as a small molecular inhibitor of FEN1 warrants further investigation.
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spelling pubmed-79409402021-03-10 FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis Xu, Lu Shen, Ji-Ming Qu, Jing-Lei Song, Na Che, Xiao-Fang Hou, Ke-Zuo Shi, Jing Zhao, Lei Shi, Sha Liu, Yun-Peng Qu, Xiu-Juan Teng, Yue-E Ann Transl Med Original Article BACKGROUND: Tamoxifen is an important choice in endocrine therapy for patients with oestrogen receptor-positive (ER+) breast cancer, and disease progression-associated resistance to tamoxifen therapy is still challenging. Flap endonuclease-1 (FEN1) is used as a prognostic biomarker and is considered to participate in proliferation, migration, and drug resistance in multiple cancers, especially breast cancer, but the prognostic function of FEN1 in ER+ breast cancer, and whether FEN1 is related to tamoxifen resistance or not, remain to be explored. METHODS: On-line database Kaplan-Meier (KM) plotter, GEO datasets, and immunohistochemistry were used to analyse the prognostic value of FEN1 in ER+ breast cancer from mRNA and protein levels. Cell viability assay and colony formation assays showed the response of tamoxifen in MCF-7 and T47D cells. Microarray data with FEN1 siRNA versus control group in MCF-7 cells were analysed by Gene Set Enrichment Analysis (GSEA). The protein levels downstream of FEN1 were detected by western blot assay. RESULTS: ER+ breast cancer patients who received tamoxifen for adjuvant endocrine therapy with poor prognosis showed a high expression of FEN1. MCF-7 and T47D appeared resistant to tamoxifen after FEN1 over-expression and increased sensitivity to tamoxifen after FEN1 knockdown. Importantly, FEN1 over-expression could activate tamoxifen resistance through the ERα/cyclin D1/Rb axis. CONCLUSIONS: As a biomarker of tamoxifen effectiveness, FEN1 participates in tamoxifen resistance through ERα/cyclin D1/Rb axis. In the future, reversing tamoxifen resistance by knocking-down FEN1 or by way of action as a small molecular inhibitor of FEN1 warrants further investigation. AME Publishing Company 2021-02 /pmc/articles/PMC7940940/ /pubmed/33708885 http://dx.doi.org/10.21037/atm-20-3068 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Xu, Lu
Shen, Ji-Ming
Qu, Jing-Lei
Song, Na
Che, Xiao-Fang
Hou, Ke-Zuo
Shi, Jing
Zhao, Lei
Shi, Sha
Liu, Yun-Peng
Qu, Xiu-Juan
Teng, Yue-E
FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis
title FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis
title_full FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis
title_fullStr FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis
title_full_unstemmed FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis
title_short FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis
title_sort fen1 is a prognostic biomarker for er+ breast cancer and associated with tamoxifen resistance through the erα/cyclin d1/rb axis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940940/
https://www.ncbi.nlm.nih.gov/pubmed/33708885
http://dx.doi.org/10.21037/atm-20-3068
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