Involvement of the Sp1 site in Ras-mediated downregulation of the RECK metastasis suppressor gene

We have isolated and characterized the 5'-flanking region of the mouse RECK gene aiming to understand the mechanism of oncogene-mediated suppression of RECK gene expression. The upstream 52-base region was found to contain a promoter activity which is, to some extent, suppressed by the ras oncogene, This region contains two Spl-binding motifs, one cEBPb-binding motif, and one CAAT box. Although both of the Spl sites were found to associate with Sp1 as well as Sp3 proteins, ras responsiveness seems to be mediated only by the downstream Sp1 site. Our data indicate that the Sp1 motif in certain contexts can serve as a negative target for the Ras signal. (C) 1999 Academic Press.