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.