ANTISENSE E1AF TRANSFECTION RESTRAINS ORAL-CANCER INVASION BY REDUCING MATRIX METALLOPROTEINASE ACTIVITIES

E1AF is a newly identified human ets-family transcription factor We ha ve reported that E1AF can up-regulate transcription of matrix metallop roteinase (MMP) genes and confers invasive phenotype on human cancer c ells. HSC3 is an oral squamous-cell-carcinoma-derived cell line, and i t manifests high levels of E1AF and MMP-1 and -9 gene expression that are associated with invasive potential, We reconstructed an E1AF antis ense expression vector, transfected HSC3 cells with the vector, and ob tained HSC3AS cells that express E1AF antisense RNA, HSC3AS showed dec reasing mRNA and protein levels of MMP-1, -3, and -9, Moreover, HSC3AS showed lower invasive potential in vitro three-dimensional raft cultu re and in vivo implantation into nude mice. These results imply that t ransfection of antisense E1AF inhibits tumor invasion by down-regulati ng MMP genes.