Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Cell Prolif. 2012 Jun;45(3):189-98. doi: 10.1111/j.1365-2184.2012.00820.x. Epub 2012 Mar 27.
The metastatic ability of breast cancer cells with chemoresistant properties is higher when compared to that of their parental wild-type cells. Expression of AnnexinA2 (Anxa2), a 36-kDa calcium-dependent phospholipid binding protein, is increased in metastatic tumours and has been found to be associated with the phenotype of drug resistance and metastasis.
In the present study, we found that up-regulation of Anxa2 correlates with enhanced migration and invasion ability of MCF-7 breast cancer cells both in vitro and in vivo. Western blot analysis revealed that exposure to chemotherapeutic drugs may induce elevated expression of Anxa2. In addition, our data have shown that Anxa2 might influence proliferation, migration and invasion of MCF-7 cells by increasing expression of c-myc and cyclin D1 via activation of Erk1/2 signalling pathways.
Our findings suggest that up-regulation of Anxa2 may play an important role in modulating proliferation and invasion of breast cancer MCF-7 cells through regulation of many relevant downstream target genes.
与亲本野生型细胞相比,具有化疗耐药性的乳腺癌细胞的转移能力更高。钙依赖性磷脂结合蛋白 36kDa(Anxa2)的表达在转移性肿瘤中增加,并且已经发现与耐药性和转移的表型相关。
在本研究中,我们发现 Anxa2 的上调与 MCF-7 乳腺癌细胞在体外和体内迁移和侵袭能力的增强相关。Western blot 分析显示,化疗药物的暴露可能诱导 Anxa2 的表达升高。此外,我们的数据表明,Anxa2 可能通过激活 Erk1/2 信号通路增加 c-myc 和细胞周期蛋白 D1 的表达来影响 MCF-7 细胞的增殖、迁移和侵袭。
我们的研究结果表明,Anxa2 的上调可能通过调节许多相关下游靶基因,在调节乳腺癌 MCF-7 细胞的增殖和侵袭中发挥重要作用。