各種成長因子によるＡＦＰ遺伝子発現の調節機構

Abstract

Alpha-fetoprotein (AFP) and albumin gene expression are specific for hepatocytes. Since liver contains not only hepatocytes but also sinusoidal lining cells such endothelial cell, Kupffer cell, Ito cell and pit cell, the liver specific gene expression may be regulated by paracrine, autocrine and endocrine mechanism. In the present study, we analyzed the factors involved in the regulation of AFP and albumin gene expression using cultured human hepatoma cell lines. Epidermal growth factor and phorbol ester synergistically suppressed the AFP enhancer activity, resulting in the down-regulation of both AFP and albumin gene expression. Hepatocyte growth factor and transforming growth factor β1 suppressed the AFP gene expression through the inhibition of its promoter activity. Δ12-Prostaglandin J2, an active form of prostaglandin D2, repressed both AFP and albumin promoter activity. AFP and albumin mRNA levels were reversibly suppressed by the increased colloid osmotic pressure. Butyric acid, a natural fermentation product of colonic bacterial flora, inhibited the proliferation of HuH-7 human hepatoma cells in conjunction with the reciprocal regulation of AFP and albumin gene expression. These results indicate that AFP gene expression as well as albumin gene expression is physiologically regulated by varing factors in a paracrine fashion or an endocrine fashion through the arterial and the portal blood flow.