Hida K, Shindoh M, Yasuda M, Hanzawa M, Funaoka K, Kohgo T, Amemiya A, Totsuka Y, Yoshida K, Fujinaga K
Department of Oral Surgery, Hokkaido University School of Dentistry, Japan.
Am J Pathol. 1997 Jun;150(6):2125-32.
E1AF is a newly identified human ets-family transcription factor. We have reported that E1AF can up-regulate transcription of matrix metalloproteinase (MMP) genes and confers invasive phenotype on human cancer cells. HSC3 is an oral squamous-cell-carcinoma-derived cell line, and it manifests high levels of E1AF and MMP-1 and -9 gene expression that are associated with invasive potential. We reconstructed an E1AF antisense expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express E1AF antisense RNA. HSC3AS showed decreasing mRNA and protein levels of MMP-1, -3, and -9. Moreover, HSC3AS showed lower invasive potential in vitro three-dimensional raft culture and in vivo implantation into nude mice. These results imply that transfection of antisense E1AF inhibits tumor invasion by down-regulating MMP genes.
E1AF是一种新发现的人类ets家族转录因子。我们曾报道E1AF可上调基质金属蛋白酶(MMP)基因的转录,并赋予人类癌细胞侵袭性表型。HSC3是一种源自口腔鳞状细胞癌的细胞系,它表现出高水平的E1AF以及与侵袭潜能相关的MMP-1和-9基因表达。我们构建了一个E1AF反义表达载体,用该载体转染HSC3细胞,获得了表达E1AF反义RNA的HSC3AS细胞。HSC3AS细胞中MMP-1、-3和-9的mRNA及蛋白水平均降低。此外,HSC3AS细胞在体外三维筏式培养及体内植入裸鼠实验中均显示出较低的侵袭潜能。这些结果表明,反义E1AF转染通过下调MMP基因抑制肿瘤侵袭。