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

The alpha 1-6 fucosylated alpha-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-beta-D-glucosaminide alpha 1-6 fucosyltransferase (alpha 1-6 FucT), an enzyme involved in the alpha 1-6 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 alpha 1-6 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 alpha 1-6 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 194 +/- 72 pmol/h/mg in HCC tissues. The mRNA expression of alpha 1-6 FucT was also enhanced in proportion to enzymatic activity except for a few cases, suggesting that alpha 1-6 FucT expression is increased in chronic liver diseases, especially liver cirrhosis. Transfection of alpha 1-6 FucT gene into cultured rat hepatocytes markedly increased alpha 1-6 FucT activity and led to an increase in lens culinaris agglutinin (LCA) binding proteins in both cell lysates and condition media. When the alpha 1-6 FucT gene was transfected into a human HCC cell line, Hep3B, which originally showed low levels of alpha 1-6 FucT expression, alpha 1-6-fucosylated AFP was dramatically increased in the condition media, Collectively, these results suggest that the enhancement of alpha 1-6 FucT expression increased the fucosylation of several proteins, including AFP, and that the level of alpha 1-6-fucosylated AFP in patients with HCC was in part caused by up-regulation of the alpha 1-6 FucT gene expression.