A single ets-related transcription factor, E1AF, confers invasive phenotype on human cancer cells.

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.