Molecular mechanisms of hereditary persistence of alpha-fetoprotein (AFP) in two Japanese families A hepatocyte nuclear factor-1 site mutation leads to induction of the AFP gene expression in adult livers

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-1alpha stimulated the activity of both the wild- and variant-type AFP promoters in hepatoma cells. HNF-1alpha 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. -->
ISSN: 1386-6346
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77636ae350a58125e81db33b4271cfed
https://pubmed.ncbi.nlm.nih.gov/15716018
Rights: CLOSED
Přírůstkové číslo: edsair.doi.dedup.....77636ae350a58125e81db33b4271cfed
Autor: Akihiro Moriuchi, Hirofumi Uto, Masatsugu Numata, Hirohito Tsubouchi, Toru Sekiya, Ildeok Kim, Akio Ido, Kenji Nagata, Katsuhiro Hayashi, Satoru Hasuike, Yoshiko Nagata-Tsubouchi
Rok vydání: 2004
Předmět:
Zdroj: Hepatology research : the official journal of the Japan Society of Hepatology. 31(2)
ISSN: 1386-6346
Popis: alpha-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-1alpha stimulated the activity of both the wild- and variant-type AFP promoters in hepatoma cells. HNF-1alpha 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.
Databáze: OpenAIRE
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