Mechanism of the dexamethasone effect on alpha-fetoprotein gene expression in McA-RH8994 rat hepatoma cells.

Abstract

We have investigated the mechanism by which dexamethasone (DEX) increases alpha-fetoprotein (AFP) secretion by the McA-RH8994 rat hepatoma cell line. In contrast to the 7777 cell line, DEX was found to increase the amount of hybridizable cytoplasmic AFP mRNA in McA-RH8994 cells. This effect was dose-dependent, reversible after removal of DEX, and was partially blocked by progesterone in excess, indicating a receptor-mediated response. In vitro nuclear transcription experiments showed that DEX increased AFP gene transcription in McA-RH8994 cells. Cycloheximide blocked the effect of DEX on AFP mRNA levels in both the McA-RH8994 and 7777 cell lines, showing that ongoing protein synthesis is required for glucocorticoids either to enhance or to suppress AFP gene expression in these cell lines.