Characterization of the 5'-flanking region of the hepatocyte growth factor gene.

The Hepatocyte growth factor is the most potent mitogen for hepatocytes in primary culture and is involved in liver regeneration. The expression of the gene appears to be tightly controlled by various humoral factors. To understand the molecular mechanism of the gene expression, we cloned and determined the nucleotide sequence of the 5'-flanking region of the gene. In this region, there are sequences homologous to responding elements of P53, Rb, IL-1, IL-6, glucocorticoids, TPA and TGF-beta. We also identified three major transcriptional initiation sites by primer extension analysis of this region. Functional analyses of this region by constructing CAT reporter plasmids indicate that the sequence functions in a tissue specific manner and there is a negative regulatory region which suppresses the gene expression in rat transformed kidney cells.