Antisense Ets-1 Transfection Restrains Oral Cancer Invasion by Reducing Matrix Metalloproteinase Activities

Abstract Ets-1 is an Ets family transcription factor, can up-regulate the transcription of matrix metalloproteinase (AMP) genes and confers an invasive phenotype on human cancer cells. HSC3 is an oral squamous cell carcinoma-derived cell line, and it manifests high levels of Ets-1 and MMP-9 gene expression that are associated with invasive potential. In this study, we investigated the effect of Ets-1 on the invasive properties of oral cancer from a molecular biological perspective. We constructed an Ets-1 antisense (AS) expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express Ets-1 AS RNA. The expression of Ets-1 and MMP-9 was analyzed with RT-PCR. The invasive ability of the HSC3AS cells was determined using a matrigel invasion assay and MMP-9 production was measured using gelatin zymography. The amount of Ets-1 mRNA was significantly reduced in HSC3AS cells compared with parental HSC3 cells and the control transfected with empty vector. Matrigel invasion assay revealed that the HSC3AS cells had lower invasive ability. Gelatin zymography demonstrated that HSC3AS MMP-9 productions were decreased compared with those of parental HSC3 cells and the control. These results imply that transfection of AS Ets-1 inhibits oral cancer invasion by down-regulating MMP-9 genes.