Yang Shan, Hui Tian-Li, Wang Hao-Qi, Zhang Xi, Mi Yun-Zhe, Cheng Meng, Gao Wei, Geng Cui-Zhi, Li Sai-Nan
Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
World J Clin Cases. 2023 Jul 16;11(20):4788-4799. doi: 10.12998/wjcc.v11.i20.4788.
Breast cancer (BC) remains a public health problem. Tamoxifen (TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.
To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.
High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.
EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.
This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.
乳腺癌（BC）仍是一个公共卫生问题。他莫昔芬（TAM）耐药给BC患者的治疗带来了很大困难。真核翻译起始因子4E结合蛋白1（EIF4EBP1）在BC的肿瘤发生和进展中起关键作用。然而，EIF4EBP1在确定TAM治疗BC患者疗效中的表达及机制仍不清楚。
研究EIF4EBP1在确定TAM治疗BC患者疗效中的表达及功能。
从基因表达综合数据库下载乳腺肿瘤的高通量测序数据。差异基因表达分析确定在癌组织中显著上调。分析其预后价值。分析其生物学功能及相关途径。随后，通过实时逆转录聚合酶链反应和蛋白质免疫印迹法测定EIF4EBP1的表达。采用细胞计数试剂盒-8法、集落形成试验和伤口愈合试验来了解EIF4EBP1的功能表型。
EIF4EBP1在TAM耐药细胞中上调，且EIF4EBP1与BC患者的预后相关。基因集富集分析表明EIF4EBP1可能参与刺猬信号通路。降低EIF4EBP1的表达可逆转TAM耐药，而EIF4EBP1的过表达则促进TAM耐药。
本研究表明EIF4EBP1在BC和TAM耐药细胞系中过表达，这增加了BC细胞的增殖、侵袭、迁移及TAM耐药性。
