Transcriptional regulation of apolipoprotein A-I expression in Hep G2 cells by phorbol ester
Résumé
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.