THE EFFECTS OF RETINOIC ACID ON THE EXPRESSION OF ALPHA-FETOPROTEIN AND ALBUMIN GENES IN RAT HEPATOMA-CELL LINES

Many transcriptional regulators can stimulate or repress gene expression depending on the cellular or genetic contexts. Thus dexamethasone increases the amount of alpha-fetoprotein mRNA in Morris rat hepatoma derived cell line McA-RH 8994 cells, but decreases it in McA-RH 7777 cells. In the present study, we demonstrated that retinoic acid, whose receptors belong to the steroid/thyroid hormone receptor gene family, also enhanced the expression of alpha-fetoprotein and albumin gene in McA-RH 8994 cells, but had no effect on alpha-fetoprotein gene expression in McA-RH 7777 cells. In contrast to the effect of dexamethasone on the alpha-fetoprotein gene expression, which requires ongoing protein synthesis, cycloheximide, a protein synthesis inhibitor, enhanced the effect of retinoic acid. Actinomycin D inhibited the retinoic acid mediated increase in alpha-fetoprotein and albumin mRNA expression. Since the McA-RH 8994 cells did not express retinoic acid receptor-beta mRNA, the observed regulatory effects of retinoic acid on alpha-fetoprotein and albumin gene expression were not mediated through retinoic acid receptor-beta. We also conclude that the regulation was at the level of transcription and that retinoic acid and dexamethasone probably regulate the expression of liver specific genes through different mechanisms.