雌激素在乳腺癌（BC）的发生中起着至关重要的作用，SUMO化引起的表观遗传修饰对于癌症的发展至关重要。然而，雌激素在蛋白质SUMO化上的作用机制以及其对BC发展的影响仍不完全了解。通过实时定量聚合酶链反应（RT-qPCR）和西方印迹法验证了BC细胞系中的SUMO1。还进行了细胞增殖和克隆形成实验，以评估由SUMO1介导的SUMO化。通过荧光酶活性来检查E2是否促进了SUMO1的转录，通过染色质免疫沉淀（ChIP）实验证明雌激素受体α（ERα）与SUMO1的结合。通过动物模型评估E2-ERα增强SUMO1转录的效果。ER阳性的BC细胞中，E2以剂量和时间依赖的方式促进SUMO1 mRNA和蛋白质表达水平的增加；它对SUMO2/3表达没有影响；在E2诱导的SUMO1转录中，ERα而不是ERβ对此过程至关重要。此外，E2-ERα通过与SUMO1启动子中一个雌激素响应元件半位点（1/2ERE，在-134至-123 bp区域内）的结合来上调SUMO1的转录，E2-ERα诱导的SUMO1转录增强了ER阳性BC细胞的细胞活性。为了进一步确定SUMO1在ER正性BC中的SUMO化作用，我们评估了新的SUMO1靶蛋白，如Ras，并证明E2通过影响下游信号通路传导增加了Ras的SUMO化和细胞增殖。最后，我们的数据揭示了E2-ERα增强SUMO1转录以促进BC原位肿瘤生长。综上，我们的结果表明，E2通过ERα与SUMO1启动子中的1/2ERE结合来促进SUMO1的转录和蛋白质表达，并且E2-ERα还增强了SUMO1介导的Ras SUMO化并介导了ER阳性BC的细胞反应。因此，我们对ER阳性BC发展的机制获得了重要的见解，并为其治疗提供了一种新的靶点。2023 Gland Surgery.版权所有。

Estrogen plays a crucial role in the tumorigenesis of breast cancer (BC), and epigenetic modification by SUMOylation is essential for cancer development. However, the mechanism underlying estrogen's actions on protein SUMOylation and its effect on BC development are still incompletely understood.SUMO1 in BC cell lines was verified via real-time quantitative PCR (RT-qPCR) and western blot. Cell proliferation and colony formation assays was also performed to evaluate SUMOylation as mediated by SUMO1. Luciferase activity to examine whether E2 promoted the transcription of SUMO1, and chromatin immunoprecipitation (ChIP) assay to determine the binding of estrogen receptor alpha (ERα) to SUMO1 were conduction, and an animal model was used to evaluate the effects of E2-ERα-enhanced SUMO1 transcription.E2 promoted SUMO1 mRNA and protein expression levels in a dose- and time-dependent manner in ER-positive BC cells; it exerted no influence on SUMO2/3 expression; in E2-induced SUMO1 transcription, ERα, but not ERβ, was essential to the process. In addition, E2-ERα upregulated the transcription of SUMO1 by binding with an estrogen-response element half-site (1/2ERE, in the -134 to -123 bp region) of the SUMO1 promoter, and E2-ERα induced SUMO1 transcription-enhanced cellular viability in ER-positive BC cells. To further determine SUMOylation as mediated by SUMO1 in ER-positive BC, we evaluated novel SUMO1 target proteins such as Ras and demonstrated that E2 increased Ras SUMOylation and cellular proliferation by affecting downstream signaling-pathway transduction. Finally, our data revealed that E2-ERα enhanced SUMO1 transcription to promote tumor growth in a BC orthotopic tumor model.Collectively, our results showed that E2 promoted the transcription and protein expression of SUMO1 via ERα binding to a 1/2ERE in the SUMO1 promoter, and that E2-ERα also augmented SUMO1-mediated Ras SUMOylation and mediated cellular responses in ER-positive BC. We therefore achieved significant insights into the mechanism involved in ER-positive BC development and provided a novel target for its treatment.2023 Gland Surgery. All rights reserved.