RECIPROCAL REGULATION OF ALPHA-FETOPROTEIN AND ALBUMIN GENE-EXPRESSION BY BUTYRATE IN HUMAN HEPATOMA-CELLS

Background/Aims: Butyrate, a product of colonic bacterial flora, functions as an antiproliferative agent and induces cell differentiation in a variety of cell types. In the present study, the effects of butyrate on cell growth and expression of α-fetoprotein (AFP) and albumin genes in HuH-7 human hepatoma cells were investigated. Methods: The HuH-7 cells were treated with sodium butyrate (0-1 mmol/L), and numbers of viable cells were counted at 24, 48, and 72 hours after treatment. To elucidate the effects of sodium butyrate on AFP and albumin gene expression, Northern blotting and transient chloramphenicol acetyltransferase plasmid transfection experiments were performed. Results: Cell growth was dose dependently inhibited by sodium butyrate. By Northern blot analysis, the level of AFP messenger RNA was reduced by treatment with sodium butyrate, whereas the level of albumin messenger RNA was elevated by this treatment. In transient chloramphenicol acetyltransferase plasmid transfection experiments, sodium butyrate repressed the AFP promoter activity but did not change the AFP enhancer or silencer activities. In contrast, the albumin promoter activity was stimulated by sodium butyrate. Conclusions: These results suggest that butyrate leads to the reciprocal differentiating regulation of AFP and albumin gene expression at the transcriptional level in human hepatoma cells. © 1994.