Kaya M, Yoshida K, Higashino F, Mitaka T, Ishii S, Fujinaga K
Department of Molecular Biology, Sapporo Medical University, School of Medicine, Japan.
Oncogene. 1996 Jan 18;12(2):221-7.
Invasion of cancer cells is the first step of metastasis. The invasive activity is thought to be dependent on the production of matrix metalloproteinases (MMPs). The transcription regulatory regions of MMP genes often contain binding sites for Ets and AP-1 transcription factors and they mediate oncogene- and growth factor-induced transcription of the genes. We recently isolated the cDNA encoding human E1AF, a new member of ets oncogene family. E1AF highly stimulated transcription from three different subclasses of MMP genes in transient expression assays. Here we show that transfection of the non-invasive human breast cancer cell line MCF-7 with the E1AF expression plasmid results in induction of invasive and motile activities, accompanied by an increase of 92 kD type IV collagenase (MMP-9) gene expression. Tumors derived from the E1AF transfectant were highly invasive and produced MMP-9. Expression of E1AF and MMP-9 genes was elevated in several invasive tumor cell lines. These results provide evidence for an important role of ets-related E1AF in tumor cell invasion.
癌细胞侵袭是转移的第一步。侵袭活性被认为依赖于基质金属蛋白酶（MMPs）的产生。MMP基因的转录调控区域通常含有Ets和AP-1转录因子的结合位点，它们介导癌基因和生长因子诱导的基因转录。我们最近分离出了编码人E1AF的cDNA，E1AF是ets癌基因家族的一个新成员。在瞬时表达试验中，E1AF强烈刺激了MMP基因三个不同亚类的转录。在此我们表明，用E1AF表达质粒转染非侵袭性人乳腺癌细胞系MCF-7会导致侵袭和运动活性的诱导，并伴随着92 kD IV型胶原酶（MMP-9）基因表达的增加。源自E1AF转染细胞的肿瘤具有高度侵袭性并产生MMP-9。在几种侵袭性肿瘤细胞系中，E1AF和MMP-9基因的表达均升高。这些结果为ets相关的E1AF在肿瘤细胞侵袭中的重要作用提供了证据。
