Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell line Hep G2

Soy phytoestrogens have been shown to increase plasma levels of HDL cholest erol and apolipoprotein (apo) A-I, its major protein component, in animal s tudies and in some human studies. The human hepatoma cell line Rep G2 was u sed to study the effect of the phytoestrogens genistein and daidzein on apo A-I secretion and gene expression in liver cells. Both genistein and daidz ein increased apo A-I secretion in a dose-dependent fashion. Apo A-I concen tration in the media of treated cells was increased approximately fivefold by 10 mu mol/L genistein (P < 0.001) and approximately onefold by 10 mu mol /L daidzein (P < 0.001) compared with control cells. The effect of genistei n on apo A-I secretion was similar to that observed with 17-beta-estradiol. Treatment of cells with genistein for 24 h increased the transcriptional a ctivity of the apo A-I gene as measured by nuclear run-on assay. Transfecti on experiments with plasmids containing regulatory regions of the apo A-I g ene cloned in front of the luciferase reporter gene indicated that the 5' r egion of the apo A-I gene contained between nucleotides -256 and -41 is res ponsible for the increased expression of this gene by genistein.