Regulation of alpha-foetoprotein gene expression by fatty acids and fibrates.
Alpha-foetoprotein (AFP), the major plasma protein in the foetus, is mainly synthesized by yolk sac and foetal liver. It binds polyunsaturated fatty acids and probably controls their metabolism and action. We investigated the effects of fatty acids and fibrates on expression of the AFP gene using two complementary approaches. Treatment with 5-8-11-14 eicosatetraynoic acid (ETYA), an analogue of arachidonic acid, specifically led to lower AFP mRNA levels in cultured rat yolk sac explants whereas treatment with palmitic or oleic acid did not. Clofibric acid and fenofibrate also gave lower AFP mRNA levels. Transient transfection experiments with HepG2 hepatoma cells showed that ETYA and clofibric acid decreased the transcriptional activity of the 7 kb regulatory region of the rat AFP gene. The 330 bp AFP promoter was identified as a target for these down regulating effects.
Bois-Joyeux
B
B
Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, CNRS, UPR 9078, Meudon, France.
Cailliau
K
K
Danan
J L
JL
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002995:Clofibric Acid / Q000494:pharmacology*; D046508:Culture Techniques; D015536:Down-Regulation / Q000235:genetics; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D014407:Tumor Cells, Cultured; D015017:Yolk Sac; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics*
D005227:Fatty Acids; D000509:alpha-Fetoproteins; D015117:5,8,11,14-Eicosatetraynoic Acid; D002995:Clofibric Acid; D011345:Fenofibrate