Duan Jing, Zhen Tiantian, Liang Jiangtao, Tang Jianming, Zhou Yu, Gao Huabin, Zhang Fenfen, Li Hui, Shi Huijuan, Han Anjia
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University Guangzhou, China.
Int J Clin Exp Pathol. 2018 Jun 1;11(6):2968-2979. eCollection 2018.
The aim of this study was to clarify the clinicopathological features and role of zinc finger protein 10 (ZNF10) in breast invasive ductal cancer (IDC). Our data first showed that ZNF10 expression was higher in 8 pairs of fresh breast IDC and breast cancer cell lines compared with their respective adjacent non-tumor breast tissues. ZNF10 expression was significantly higher in IDC compared with DCIS and fibroadenoma of the breast. ZNF10 expression was significantly associated with patients' age, tumor stage, and breast cancer molecular subtype. ZNF10 knockdown inhibited breast cancer cell proliferation, colony formation, cell cycle progression, cell migration, and invasion but induced apoptosis. ZNF10 knockdown also suppressed the tumorigenicity of breast cancer in vivo. The underlying mechanism study showed that ZNF10 regulated the β-catenin signaling pathway in breast cancer. ZNF10 might bind to the region (nucleotides -300 to +100) of the β-catenin promoter. In conclusion, our results first suggest that ZNF10 promotes the carcinogenesis and progression of breast IDC via the β-catenin signaling pathway. Targeting ZNF10 might be a novel treatment strategy for breast cancer.
本研究的目的是阐明锌指蛋白10（ZNF10）在乳腺浸润性导管癌（IDC）中的临床病理特征及作用。我们的数据首次表明，与各自相邻的非肿瘤乳腺组织相比，8对新鲜乳腺IDC组织和乳腺癌细胞系中ZNF10的表达更高。与乳腺导管原位癌（DCIS）和纤维腺瘤相比，ZNF10在IDC中的表达显著更高。ZNF10的表达与患者年龄、肿瘤分期及乳腺癌分子亚型显著相关。敲低ZNF10可抑制乳腺癌细胞增殖、集落形成、细胞周期进程、细胞迁移和侵袭，但可诱导细胞凋亡。敲低ZNF10还可在体内抑制乳腺癌的致瘤性。潜在机制研究表明，ZNF10在乳腺癌中调节β-连环蛋白信号通路。ZNF10可能与β-连环蛋白启动子的区域（核苷酸-300至+100）结合。总之，我们的结果首次表明，ZNF10通过β-连环蛋白信号通路促进乳腺IDC的发生和进展。靶向ZNF10可能是一种新的乳腺癌治疗策略。
