DKK-1通过上调nm23表达抑制乳腺癌细胞迁移  

Dickkopf-1 Inhibits Migration in Breast Cancer Cells via Upregulating nm23

作　　者：周晓雷[1] 张晓东[1] 叶丽虹[1] 

机构地区：[1]南开大学生命科学学院教育部生物活性材料重点实验室,天津300071

出　　处：《中国生物化学与分子生物学报》2010年第2期164-169,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.30770826);天津市科委攻关培育基金(No.08JCZDJC20700)资助~~

摘　　要：Dickkopf-1(DKK-1)作为Wnt/β-连环蛋白(Wnt/β-catenin)经典信号传导通路的拮抗剂而受到关注.为了进一步阐明DKK-1在乳腺癌细胞迁移中的作用及其分子机制,应用我们建立的乳腺癌细胞MCF-7高转移倾向亚克隆LM-MCF-7细胞株,比较了DKK-1在不同转移能力的乳腺癌细胞株中表达水平及其与细胞迁移能力的关系.结果显示,DKK-1在LM-MCF-7细胞中表达明显下调;"伤口愈合"实验结果表明,在MCF-7细胞中,RNA干扰DKK-1可导致细胞迁移能力增强;相反,在LM-MCF-7细胞中过表达DKK-1则可抑制细胞的迁移.进一步研究结果显示,DKK-1为肿瘤转移抑制因子nm23的上游激活因子.因此,我们的研究结果表明,DKK-1表达水平下调导致nm23表达水平下调,解除了对乳腺癌细胞迁移的抑制作用,是LM-MCF-7乳腺癌细胞具有高迁移能力的原因之一;反之,与LM-MCF-7相比,DKK-1在MCF-7细胞中高表达,其通过上调nm23可抑制乳腺癌细胞迁移.这一发现对进一步揭示乳腺癌细胞转移的分子机制具有的重要意义.Dicckkopf-1（DKK-1）,an inhibitor of Wnt/β-catenin signaling,plays an important role in tumor metastasis.In the present study,we examined the expression of DKK-1 in MCF-7 and LM-MCF-7 cells（a metastatic subclone of MCF-7 cells） with different migrating potentials to demonstrate the role of DKK-1 in migration of breast cancer cells.Western blot analysis and wound healing assay showed that the expression of DKK-1 was negatively related to the migration ability of breast cancer cells.Moreover,we found that DKK-1 was an upstream activator of nm23,a tumor metastasis suppressor gene.Thus,our data revealed that the downregulation of DKK-1 in LM-MCF-7 cells resulted in the downregulation of nm23,which led to the losing control of the migration of breast cancer cells.It is one of the reasons of high migration ability of LM-MCF-7 breast cancer cells.While,the DKK-1 was upregulated in MCF-7 cells relative to LM-MCF-7 cells,resulting in the upregulation of nm23,which inhibited the migration of breast cancer cells.The finding is significant for exploring the molecular mechanism of metastasis in breast cancer cells.

关 键 词：DICKKOPF-1 NM23 乳腺癌 细胞迁移 

分 类 号：Q25[生物学—细胞生物学] Q51