دورية أكاديمية
FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis.
| العنوان: | FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis. |
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| المؤلفون: | Xu L; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Shen JM; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Qu JL; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Song N; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Che XF; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Hou KZ; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Shi J; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Zhao L; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Shi S; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Liu YP; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Qu XJ; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China., Teng YE; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China. |
| المصدر: | Annals of translational medicine [Ann Transl Med] 2021 Feb; Vol. 9 (3), pp. 258. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: AME Publishing Company Country of Publication: China NLM ID: 101617978 Publication Model: Print Cited Medium: Print ISSN: 2305-5839 (Print) Linking ISSN: 23055839 NLM ISO Abbreviation: Ann Transl Med Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Hong Kong] : AME Publishing Company |
| مستخلص: | 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. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3068). The authors have no conflicts of interest to declare. (2021 Annals of Translational Medicine. All rights reserved.) |
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| فهرسة مساهمة: | Keywords: Estrogen receptor positive (ER+) breast cancer; Flap endonuclease-1 (FEN1); prognostic biomarker; tamoxifen resistance |
| تواريخ الأحداث: | Date Created: 20210312 Latest Revision: 20220421 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7940940 |
| DOI: | 10.21037/atm-20-3068 |
| PMID: | 33708885 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2305-5839 |
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| DOI: | 10.21037/atm-20-3068 |