Transcriptional regulation of apolipoprotein A-I expression in Hep G2 cells by phorbol ester.
The regulation of apolipoprotein A-I (apo A-I) gene expression by 12-O-tetradecanoylphorbol 13-acetate (TPA) was investigated in the human hepatoma cell line Hep G2. TPA treatment decreased apo A-I mRNA levels in a time-dependent manner, by up to 50% versus control cells within 24 h. Nuclear run-on transcription assays demonstrated a transcriptional effect of TPA. Using transfection analysis with a plasmid construct containing the -1378/+11 apo A-I promoter fused to the secreted placental alkaline phosphatase (SPAP) reporter gene, we showed that the SPAP activity was decreased to 50% when Hep G2 cells were incubated in the presence of TPA. The inhibitory effect of TPA was still maintained when fragment -253 to -4 of apo A-I promoter was linked to the CAT reporter gene. These data indicate that transcriptional modulation of apolipoprotein A-I gene expression following phorbol ester treatment is transduced by gene elements located between -253 and -4 of the apo A-I promoter.
CNRS URA 1283, CHU Saint Antoine, Paris, France.
Y
Y
Vandenbrouck
G
G
Lambert
B
B
Janvier
D
D
Girlich
G
G
Bereziat
M
M
Mangeney-Andreani
D016632:Apolipoprotein A-I / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection / Q000235:genetics
D016632:Apolipoprotein A-I; D013755:Tetradecanoylphorbol Acetate