[摘要] 目的：探讨TET1 催化结构域（TET1-CD）基因高表达对乳腺癌细胞MDA-MB-231 增殖、迁移的影响及其可能的作用机制。方法：慢病毒感染建立高表达TET1-CD的MDA-MB-231 细胞系，用qPCR检测细胞中TET1-CD mRNA的表达，Transwell实验和细胞划痕实验检测细胞的迁移能力，MTT 法和克隆形成实验检测细胞的增殖能力，WB实验检测MDA-MB-231 细胞上皮间质转化（EMT）途径相关蛋白E-cadherin、Vimentin、MMP2 以及Wnt、Hedgehog(HH)通路相关蛋白的表达水平。结果：过表达TET1-CD提高乳腺癌MDA-MB-231 细胞TET1-CD的表达水平（P<0.01），明显抑制MDA-MB-231 细胞的增殖和迁移能力（均P<0.01）。过表达TET1-CD 可使乳腺癌MDA-MB-231 细胞E-cadherin 表达上升，Vimentin、MMP2 表达下调（均P<0.05）；可使β-catenin、C-myc、CyclinD1、Gli1 蛋白表达水平降低（均P<0.05）。结论：过表达TET1-CD可能通过Wnt、HH信号通路抑制EMT途径进而抑制乳腺癌细胞MDA-MB-231 的增殖和迁移。

[Abstract] Objective: To investigate the effect of high expression of TET1 catalytic domain (TET1-CD) gene on the proliferation and migration of breast cancer MDA-MB-231 cells and its underlying mechanism. Methods: MDA-MB-231 cell line with high TET1-CD expression was established by lentiviral transfection. Real-time quantitative PCR was used to detect the mRNA expression of TET1-CD.Transwell assay and cell scratch assay were used to detect cell migration ability, MTT assay and colony formation assay were used to detect cell proliferation capacity. And WB was adopted to detect the expressions of EMT-related proteins (E-cadherin, Vimentin, MMP2)and Wnt, Hedgehog pathway-related proteins in MDA-MB-231 cells. Results: The MDA-MB-231 cell line with high TET1-CD expression was successfully constructed (all P<0.01). TET1-CD over-expression significantly inhibited the proliferation and migration of breast cancer MDA-MB-231 cells (P<0.01); in addition, TET1-CD over-expression increased the expression of E-cadherin, but down-regulated the expressions of Vimentin, MMP2, β -catenin, Gli1, C-myc and CyclinD1 (all P<0.05). Conclusion: TET1-CD may inhibit the proliferation and migration of breast cancer MDA-MB-231 cells by inhibiting the EMT through Wnt and HH signaling pathway.

国家自然科学基金资助项目（No.21677006）；北京市科委基金资助项目（No.K2015311201501）