TRAIL 蛋白与其同源死亡受体 (DR) 结合后可以特异性诱导乳腺肿瘤细胞凋亡，而不会影响正常细胞。然而，TRAIL 也与诱饵受体 (DCR) 结合，从而抑制细胞凋亡途径，从而导致 TRAIL 抗性。此外，基于 TRAIL 的疗法无法获得 FDA 批准的障碍之一可能是因为对治疗的耐药性。因此，在当前的研究中，我们希望探讨转录因子在乳腺癌 TRAIL 耐药中的作用。重新分析 TRAIL 敏感（TS）和 TRAIL 耐药（TR）MDA-MB-231 细胞的微阵列数据，然后使用定量PCR (qPCR)、免疫印迹和免疫荧光技术验证候选基因。在 MDA-MB-231 和 MCF7 细胞中进行候选基因的过表达，然后进行细胞活力测定和裂解 caspase-3 的免疫印迹。此外，还进行了 DCR2 的免疫印迹。 TCGA 乳腺癌患者存活率用于 Kaplan-Meier (KM) 图。使用 qPCR 和免疫印迹对候选基因（即 ELF3）进行验证，结果显示与 TS 细胞相比，TR 细胞中该基因的表达下调。使用细胞活力测定和 cleaved caspase-3 免疫印迹观察到，MDA-MB-231 和 MCF7 细胞中 ELF3 过表达导致 TRAIL 耐药性逆转。 ELF3 过表达还导致 MDA-MB-231 和 MCF7 细胞中 DCR2 下调。此外，KM 分析发现高 ELF3 和低 DCR2 表达在 TRAIL 存在下显示出更好的患者生存率。我们的研究表明 ELF3 是影响 TRAIL 介导的乳腺癌细胞凋亡的重要因素。此外，在设计基于 TRAIL 的成功治疗策略时，应考虑 ELF3 和 DCR2 表达状态。© 2024。作者获得 Springer Nature B.V. 的独家许可。

TRAIL protein on binding to its cognate death receptors (DR) can induce apoptosis specifically in breast tumor cells sparing normal cells. However, TRAIL also binds to decoy receptors (DCR) thereby inhibiting the apoptotic pathways thus causing TRAIL resistance. Also, one of the barriers due to which TRAIL-based therapy could not become FDA-approved might be because of resistance to therapy. Therefore, in the current study we wanted to explore the role of transcription factors in TRAIL resistance with respect to breast cancer.Microarray data from TRAIL-sensitive (TS) and TRAIL-resistant (TR) MDA-MB-231 cells were reanalyzed followed by validation of the candidate genes using quantitative PCR (qPCR), immunoblotting and immunofluorescence technique. Overexpression of the candidate gene was performed in MDA-MB-231 and MCF7 cells followed by cell viability assay and immunoblotting for cleaved caspase-3. Additionally, immunoblotting for DCR2 was carried out. TCGA breast cancer patient survival was used for Kaplan-Meier (KM) plot.Validation of the candidate gene i.e. ELF3 using qPCR and immunoblotting revealed it to be downregulated in TR cells compared to TS cells. ELF3 overexpression in MDA-MB-231 and MCF7 cells caused reversal of TRAIL resistance as observed using cell viability assay and cleaved caspase-3 immunoblotting. ELF3 overexpression also resulted in DCR2 downregulation in the MDA-MB-231 and MCF7 cells. Furthermore, KM analysis found high ELF3 and low DCR2 expression to show better patient survival in the presence of TRAIL.Our study shows ELF3 to be an important factor that can influence TRAIL-mediated apoptosis in breast cancer. Also, ELF3 and DCR2 expression status should be taken into consideration while designing strategies for successful TRAIL-based therapy.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.