Functional elucidation and methylation-mediated downregulation of ITGA5 gene in breast cancer cell line MDA-MB-468.

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. Published 2010 Wiley-Liss, Inc.