Transcriptional Regulation Of Cyp3a7 By P53.

Purpose CYP3A7 gene expression is increased in some adults as those with hepatocellular carcinoma, although this P450 is dominant with fetus or neonate, while CYP3A4 dominant with normal adult. We hypothesized the discrepancy of promoter sequence in up-stream between these P450 genes play important role, and attempted to investigate this in the cell line, especially focusing on p53. Method (1) HepG2 and Huh7 (human hepatocellular carcinoma), Huh6 (hepatoblastoma), and other cancer cell lines were purchased and cultured to examine the expression of CYP3A7 mRNA and p53 protein. (2) p53 sense (SE) and p53 antisense (AS) were designed by the human p53 cDNA sequence report (GenBank), and of those influence in HepG2 cells on expression of CYP3A7 mRNA, CYP3A4 mRNA with RT-PCR method, and also of p53 protein with Western blot analysis were analyzed, respectively. Results: (1) HepG2 and Huh7 cell line expressed increased CYP3A7 mRNA and p53 protein, while other cell lines did not remarkably. (2) p53 AS decreased CYP3A7 mRNA and p53, while not with p53 SE in HepG2 cells. Discussion There is p53 recognizing region in up-stream of 5′ promoter region of CYP3A7 gene (-328 to -337bp), though not of CYP3A4 gene. This fact and the present results will suggest the importance of p53 in CYP3A7 regulation in liver tissue. Clinical Pharmacology & Therapeutics (2004) 75, P17–P17; doi: 10.1016/j.clpt.2003.11.063