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Molecular mechanisms of hereditary persistence of α-fetoprotein (AFP) in two Japanese families: A hepatocyte nuclear factor-1 site mutation leads to induction of the AFP gene expression in adult livers
- Source :
- Hepatology Research; Feb2005, Vol. 31 Issue 2, p81-89, 9p
- Publication Year :
- 2005
-
Abstract
- Abstract: α-Fetoprotein (AFP) is produced abundantly in fetal liver but is hardly detectable in adults. In this study, we investigated two unrelated Japanese families with hereditary persistence of AFP. A g→a substitution at nucleotide −119 (−119g→a) in the hepatocyte nuclear factor (HNF)-1 binding site of the AFP promoter was identified in both families. The activity of the wild- or variant-type human AFP promoter was evaluated by in vitro and in vivo transfection experiments. This substitution in the AFP promoter significantly stimulated its transcriptional activity in human hepatoma cells, regardless of their prior AFP production. The variant-type AFP promoter was also active in adult mouse livers in vivo. Additionally, overexpression of HNF-1α stimulated the activity of both the wild- and variant-type AFP promoters in hepatoma cells. HNF-1α expression also activated both AFP promoters even in nonhepatoma cells, and this activation was suppressed by nuclear factor (NF)-I overexpression. These results indicate that an HNF-1 binding site mutation leads to induction of the AFP gene expression in adult liver, and suggest that competition between HNF-1 and NF-I in this region is involved in transcriptional regulation of the AFP gene during hepatic development. [Copyright &y& Elsevier]
- Subjects :
- LIVER diseases
GENETIC disorders
NUCLEOTIDES
HEPATOCELLULAR carcinoma
CELLS
Subjects
Details
- Language :
- English
- ISSN :
- 13866346
- Volume :
- 31
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Hepatology Research
- Publication Type :
- Academic Journal
- Accession number :
- 17523117
- Full Text :
- https://doi.org/10.1016/j.hepres.2004.12.002