乳腺癌是一种经常被诊断的癌症，也是全球女性死亡的主要原因。肿瘤相关巨噬细胞会刺激细胞因子和化学趋化因子的产生，导致血管生成、转移、增殖和肿瘤浸润免疫细胞。尽管白细胞介素-32（IL-32）在多种癌症的发展和调节中有所涉及，但其在乳腺癌中的功能尚不明确。通过Sanger测序在乳腺癌患者的组织中检测到白细胞介素-32θ（IL-32θ）的突变。使用RT-qPCR检测炎症因子、趋化因子和介质的mRNA水平。使用相应的酶联免疫吸附实验检测分泌的蛋白质。使用MTS测定、迁移实验和Western blotting评估突变IL-32θ对乳腺癌细胞增殖、迁移、上皮间质转化（EMT）和细胞周期停滞的抑制作用。在乳腺肿瘤和相邻正常组织中检测到白细胞介素-32θ的一个点突变（281C>T, Ala94Val），该突变抑制了炎症因子、EMT因子和与细胞周期相关因子的表达。突变的IL-32θ通过调节NF-κB通路抑制了炎症因子的表达。此外，突变的IL-32θ通过FAK/PI3K/AKT通路抑制了EMT标志物和与细胞周期相关的因子。这说明突变的IL-32θ调节了乳腺癌的进展。突变的IL-32θ（A94V）通过调节NF-κB（p65/p50）和FAK-PI3K-GSK3通路抑制了乳腺癌中的炎症、EMT和增殖。© 2023国际生物化学与分子生物学联合会。

Breast cancer is a frequently diagnosed cancer and the leading cause of death among women worldwide. Tumor-associated macrophages stimulate cytokines and chemokines, which induce angiogenesis, metastasis, proliferation, and tumor-infiltrating immune cells. Although interleukin-32 (IL-32) has been implicated in the development and modulation of several cancers, its function in breast cancer remains elusive. Mutation of interleukin-32θ (IL-32θ) in the tissues of patients with breast cancer was detected by Sanger sequencing. RT-qPCR was used to detect the mRNA levels of inflammatory cytokines, chemokines, and mediators. The secreted proteins were detected using respective enzyme-linked immunosorbent assays. Evaluation of the inhibitory effect of mutant IL-32θ on proliferation, migration, epithelial-mesenchymal transition (EMT), and cell cycle arrest in breast cancer cells was conducted using MTS assays, migration assays, and Western blotting. A point mutation (281C>T, Ala94Val) was detected in IL-32θ in both breast tumors and adjacent normal tissues, which suppressed the expression of pro-inflammatory factors, EMT factors, and cell cycle related factors. Mutated IL-32θ inhibited the expression of inflammatory factors by regulating the NF-κB pathway. Furthermore, mutated IL-32θ suppressed EMT markers and cell cycle related factors through the FAK/PI3K/AKT pathway. It was inferred that mutated IL-32θ modulates breast cancer progression. Mutated IL-32θ (A94V) inhibited inflammation, EMT, and proliferation in breast cancer by regulating the NF-κB (p65/p50) and FAK-PI3K-GSK3 pathways.© 2023 International Union of Biochemistry and Molecular Biology.