Serum induces a transcriptional activation of CYP1A1 gene in HepG2 independently of the AhR pathway.
CYP1A1 is largely implicated in carcinogenesis. To date, it is known that this gene is induced by xenobiotics such as polycyclic aromatic hydrocarbons. In this study, we evaluated the effect of serum in the regulation of CYP1A1 gene expression. CYP1A1 mRNA level is induced 1) in HepG2 and HT29-D4 cells by 3-methylcholanthrene 2) only in HepG2 after treatment by serum. The CYP1A1 mRNA induction in HepG2 is the consequence at least in part of a transcriptional activation as was demonstrated by evaluation of the hnRNA level. HepG2 cells were transfected by a plasmid containing the 7.5 Kb of the CYP1A1 promoter and the CAT reporter gene. No CAT stimulation was observed after serum treatment. These results demonstrated that CYP1A1 is induced at a transcriptional level by a physiological compound contained in serum independently of the Ah receptor and the 7.5 Kb promoter region.
Guigal
N
N
UPRES A CNRS 6032, Faculté de Pharmacie, Marseille, France.
Seree
E
E
Nguyen
Q B
QB
Charvet
B
B
Desobry
A
A
Barra
Y
Y
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D001769:Blood; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002417:Cattle; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003110:Colonic Neoplasms / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology; D012332:RNA, Heterogeneous Nuclear / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018336:Receptors, Aryl Hydrocarbon; D012710:Serum Albumin, Bovine; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; D015500:Chloramphenicol O-Acetyltransferase