Differential Regulation of Albumin Gene Expression by Heparin-Binding Epidermal Growth Factor-Like Growth Factor in α-Fetoprotein-Producing and -Nonproducing Human Hepatoma Cells

Abstract

The effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on albumin gene expression were analyzed in α-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 selectively suppressed the AFP enhancer activity, resulting in decreased levels 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 regulating both the albumin and AFP promoters, and that HB-EGF downregulates the albumin gene expression only in the absence of the AFP silencer through the repression of the AFP enhancer activity.