Differential regulation of albumin gene expression by heparin-binding epidermal growth factor-like growth factor in alpha-fetoprotein-producing and -nonproducing human hepatoma cells

The effects of heparin-binding epidermal growth factor-like growth factor ( HB-EGF) on albumin gene expression were analyzed in alpha-fetoprotein (AFP) -producing and AFP-nonproducing human hepatoma cells, HuH-7 and huH-1/cl.2, in which the AFP silencer is inactive and active, respectively. HB-EGF sel ectively suppressed the AFP enhancer activity, resulting in decreased level s of both albumin and AFP mRNA in HuH-7 cells. In contrast, HB-EGF did not influence the albumin transcripts in huH-1/cl.2 cells or primary culture of rat hepatocytes, although the AFP enhancer activity was reduced by HB-EGF in huH-1/cl.2 cells as well as in HuH-7 cells. These results indicate that the AFP silencer interacts with the AFP enhancer to block its activity regu lating both the albumin and AFP promoters, and that HB-EGF downregulates th e albumin gene expression only in the absence of the AFP silencer through t he repression of the AFP enhancer activity.