Mechanism of the dexamethasone effect on alpha-fetoprotein gene expression in McA-RH8994 rat hepatoma cells.
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.
Cook
J R
JR
Chiu
J F
JF
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D000509:alpha-Fetoproteins / Q000235:genetics*
D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D011374:Progesterone; D003907:Dexamethasone