Gene expression of α1-6 fucosyltransferase in human hepatoma tissues: A possible implication for increased fucosylation of α-fetoprotein

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Abstract
The α1-6 fucosylated α-fetoprotein (AFP) present in serum of patients with hepatocellular carcinoma (HCC) has been employed for the differential clinical diagnosis of HCC from chronic liver diseases. The molecular mechanism by which this alteration occurs, however, remains largely unknown. To address this issue, we purified GDP-l -Fuc:N-acetyl-β-d-glucosaminide α1-6 fucosyltransferase (α1-6 FucT), an enzyme involved in the α1-6 fucosylation of N-glycans from porcine brain, as well as from a human gastric cancer cell line, and cloned their genes. In this study, levels of α1-6 FucT mRNA expression and the activity of this enzyme for 12 human HCC tissues were examined and compared with that in surrounding tissues and normal livers. The mean ± SD for α1-6 FucT activity was 78 ± 41 pmol/h/mg in normal control liver, 202 ± 127 pmol/h/mg in adjacent uninvolved liver tissues (chronic hepatitis: 181 ± 106 pmol/h/mg; liver cirrhosis: 233 ± 164 pmol/h/mg), and 195 ± 72 pmol/h/mg in HCC tissues. The mRNA expression of α1-6 FucT was also enhanced in proportion to enzymatic activity except for a few cases, suggesting that α1-6 FucT expression is increased in chronic liver diseases, especially liver cirrhosis. Transfection of α1-6 FucT gene into cultured rat hepatocytes markedly increased α1-6 FucT activity and led to an increase in lens culinaris agglutinin (LCA) binding proteins in both cell lysates and condition media. When the α1-6 FucT gene was transfected into a human HCC cell line, Hep3B, which originally showed low levels of α1-6 FucT expression, α1-6-fucosylated AFP was dramatically increased in the condition media. Collectively, these results suggest that the enhancement of α1-6 FucT expression increased the fucosylation of several proteins, including AFP, and that the level of α1-6-fucosylated AFP in patients with HCC was in part caused by up-regulation of the α1-6 FucT gene expression.

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