CHARACTERIZATION OF THE SCATTER FACTOR HEPATOCYTE GROWTH-FACTOR GENE PROMOTER - POSITIVE AND NEGATIVE REGULATORY ELEMENTS DIRECT GENE-EXPRESSION TO MESENCHYMAL CELLS

Scatter factor/hepatocyte growth factor (SF/HGF) and its receptor c-Me t represent a paracrine signaling system involved in mesenchymal-epith elial interactions during development and during tumor progression. We have examined the promoters of the mouse and human SF/HGF genes by de letion mapping followed by CAT assays as well as by gel retardation an d footprinting analysis. The promoter sequences are highly conserved ( 89.5% identity) up to position -453 from the major transcription start site but diverged considerably further upstream. Both promoters are a ctive in mesenchymal but not epithelial cells thus reflecting the expr ession pattern of the SF/HGF gene in cells in vitro and in vivo. We ha ve here identified two regulatory sequences in the SF/HGF promoter: a negative element at positions -239 to -258 and a positive element near the major transcription start site; specific deletions destroyed the activities of these elements. We were not able to localize elements on the SF/HGF promoter region that mediate the previously described effe cts of transforming growth factor beta, 12-O-tetradecanoylphorbol-13-a cetate, and coculture of epithelial cells on SF/HGF gene expression. T his study represents a first step toward understanding the intricately regulated and cell type-specific expression of the paracrine acting S F/HGF.