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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.
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.
Afiliación
  • Xu L; Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.
  • Shen JM; 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.
  • Song N; 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.
  • Hou KZ; 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.
  • Zhao L; 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.
  • Liu YP; 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.
  • Teng YE; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China.
Ann Transl Med ; 9(3): 258, 2021 Feb.
Article en En | MEDLINE | ID: mdl-33708885
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Ann Transl Med Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Ann Transl Med Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: China