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

ABSTRACT

<I>Ets-1</I> is an <I>Ets</I> family transcription factor, can up-regulate the transcription of matrix metalloproteinase (MMP) 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 <I>Ets-1</I> and <I>MMP-9</I> gene expression that are associated with invasive potential. In this study, we investigated the effect of <I>Ets-1</I> on the invasive properties of oral cancer from a molecular biological perspective. We constructed an <I>Ets-1</I> antisense (AS) expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express <I>Ets-1</I> AS RNA. The expression of <I>Ets-1</I> and <I>MMP-9</I> was analyzed with RT-PCR. The invasive ability of the HSC3AS cells was determined using a matrigel invasion assay and <I>MMP-9</I> production was measured using gelatin zymography. The amount of <I>Ets-1</I> 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 <I>Ets-1</I> inhibits oral cancer invasion by down-regulating <I>MMP-9</I> genes.