Aberrant methylation of integrin α4 gene in human gastric cancer cells

Publisher Website
Google Scholar
Abstract
Integrins are adhesion receptors that mediate both cell–extracellular matrix and cell–cell interactions. It has also been reported that the loss of integrin 4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been explored. In the present study, we found that the integrin 4 expression is lost in human gastric cancer cell lines and that this is recovered by treatment with DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. Methylation-specific PCR (MSP) and bisulfite genomic DNA sequencing demonstrated the CpG methylation-dependent silencing of integrin 4 expression in eight of nine (88.8%) gastric cancer cell lines and in 84.7% of 46 primary tumors. We also investigated whether the restoration of integrin 4 in integrin 4-inactivated cells affects their ability to invade extracellular matrix, using matrigel assays. Interestingly, integrin 4-stable transfectants had markedly less invasive ability than the parental cells. Taken together, these results suggest that the transcriptional repression of the integrin 4 gene is caused by aberrant DNA methylation, and that this may play an important role in human gastric carcinogenesis.