Department of Breast Surgery, Zhengzhou Central Hospital Affliated to Zhengzhou University, Zhengzhou, Henan, China.
Environ Toxicol. 2024 Nov;39(11):5162-5172. doi: 10.1002/tox.24373. Epub 2024 Aug 7.
Estrogen receptor α (ERα) promotes the growth and survival of ER-positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin-bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER-associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER-positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3β pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC.
雌激素受体 α（ERα）促进 ER 阳性乳腺癌（BC）细胞的生长和存活。ER 通过与雌激素结合激活后，通过直接结合特定的雌激素反应元件来调节 ER 表达的靶基因。在这项研究中，使用 RIME 方法鉴定了 MCF7 乳腺癌细胞系中与内源性染色质结合的 ER 相互作用的 106 种蛋白质。相互作用组数据表明，包含 28 个三肽基序的三聚体基序（TRIM28）是最显著富集的 ER 相关蛋白。这项研究提供了证据表明，TRIM28 的表达提高了 ER 的转录活性，并促进了 BC 细胞的增殖、迁移和侵袭。TRIM28 的高表达与 ER 阳性 BC 患者的不良临床结局相关。机制实验表明，TRIM28 表达激活 AKT/GSK3β 通路。总之，TRIM28 作为 ER 和 AKT 信号的调节蛋白；因此，它可以作为 BC 治疗干预的靶点。
