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

  • Nagata-Tsubouchi Y
  • Ido A
  • Uto H
 et al. 
  • 5

    Readers

    Mendeley users who have this article in their library.
  • 13

    Citations

    Citations of this article.

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. © 2004 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Hepatocyte nuclear factor-1
  • Hereditary persistence of AFP
  • Hydrodynamic-based gene transfer
  • Nuclear factor-I
  • Transcription
  • α-Fetoprotein

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Yoshiko Nagata-Tsubouchi

  • Akio Ido

  • Hirofumi Uto

  • Masatsugu Numata

  • Akihiro Moriuchi

  • Ildeok Kim

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free