Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
Int J Oncol. 2020 Sep;57(3):707-720. doi: 10.3892/ijo.2020.5084. Epub 2020 Jun 19.
The function of activating transcription factor 3 (ATF3) in cancer is context‑dependent and its role in endometrial carcinoma (EC) is yet to be elucidated. In the present study, ATF3 was indicated to be downregulated, while one of the ATF3‑interacting proteins, JunB, was upregulated in ECs according to western blot analysis. After overexpression in ECs, ATF3 inhibited the proliferation and invasion of EC cells and enhanced apoptosis, as well as suppressed the expression of JunB. The properties of EC cells, including the expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, the cell cycle and apoptosis were all altered by overexpression of ATF3. Furthermore, luciferase activity assay, chromatin precipitation and DNA affinity assay results indicated that ATF3 exerted the aforementioned functions via JunB binding and activator protein‑1 signaling. However, the interaction between ATF3 and JunB did not occur in EC cells under basal conditions, but in ATF3‑overexpressing ECs, which was capable of mitigating EC proliferation, invasion and metastasis. Collectively, the present results suggested that the ATF3/JunB interaction may serve as a potential therapeutic target for ECs.
激活转录因子 3（ATF3）在癌症中的功能具有上下文依赖性，其在子宫内膜癌（EC）中的作用尚待阐明。在本研究中，根据 Western blot 分析表明，ATF3 在 EC 中呈下调表达，而 ATF3 相互作用蛋白之一 JunB 呈上调表达。在 EC 中过表达后，ATF3 抑制 EC 细胞的增殖和侵袭，并促进细胞凋亡，同时抑制 JunB 的表达。EC 细胞的特性，包括基质金属蛋白酶和金属蛋白酶组织抑制剂的表达、细胞周期和凋亡均通过 ATF3 的过表达而改变。此外，荧光素酶活性测定、染色质沉淀和 DNA 亲和测定结果表明，ATF3 通过 JunB 结合和激活蛋白-1 信号传导发挥上述功能。然而，在基础条件下，ATF3 和 JunB 之间的相互作用不会发生在 EC 细胞中，而是在过表达 ATF3 的 EC 细胞中发生，这能够减轻 EC 的增殖、侵袭和转移。综上所述，本研究结果表明，ATF3/JunB 相互作用可能成为 EC 的潜在治疗靶点。
