Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen, PR China.
J Cell Biochem. 2010 Aug 1;110(5):1130-41. doi: 10.1002/jcb.22626.
Expression level of integrin alpha5 in tumor cells has been indicated to be involved in cell proliferation and organ-specific metastasis. We previously demonstrated that ITGA5 expression was downregulated in the high invasive MDA-MB-468 cells compared with other breast cancer cell lines. In this study, we found that the methylation status in the region around transcriptional start site of ITGA5 gene was increased in MDA-MB-468 cells. Overexpression of integrin alpha5 on MDA-MB-468 cells resulted in cell growth inhibition, which could be reversed by adhesion to fibronectin. Cell adhesion and spreading to fibronectin was enhanced after ITGA5 was overexpressed in MDA-MB-468 cells, while cell migration was attenuated. Knockdown of ITGA5 in MCF-7 cells led to cell growth inhibition but had little influence on cell migration. These findings indicated the diverse roles of ITGA5 expression in breast cancer cells.
肿瘤细胞中整合素 α5 的表达水平被表明与细胞增殖和器官特异性转移有关。我们之前的研究表明,与其他乳腺癌细胞系相比,高侵袭性 MDA-MB-468 细胞中 ITGA5 的表达下调。在这项研究中,我们发现 ITGA5 基因转录起始位点周围区域的甲基化状态在 MDA-MB-468 细胞中增加。在 MDA-MB-468 细胞中过表达整合素 α5 导致细胞生长抑制,而这种抑制可以通过黏附到纤维连接蛋白来逆转。在 MDA-MB-468 细胞中过表达 ITGA5 后,细胞黏附和铺展到纤维连接蛋白的能力增强,而细胞迁移能力减弱。在 MCF-7 细胞中敲低 ITGA5 导致细胞生长抑制,但对细胞迁移几乎没有影响。这些发现表明 ITGA5 表达在乳腺癌细胞中的作用是多样化的。