High expression of alpha-1-6 fucosyltransferase during rat hepatocarcinogenesis.

Abstract

Alpha-1-6 fucosylated alpha-fetoprotein (AFP) is known to be elevated in patients with primary hepatoma and has been suggested as being useful as an early indicator and predictor of the poor prognosis for hepatoma. Although GDP-L-fucosyl-N-acetyl-beta-D-glucosaminide alpha-1-6 fucosyltransferase (alpha-1-6 FucT), is the key enzyme involved in alpha-1-6 fucosylation of AFP, when and how the expression of alpha-1-6 FucT is enhanced during hepatocarcinogenesis is unknown. Recently, we established a convenient assay method for this enzyme and were successful in the purification and cDNA cloning of alpha-1-6 FucT from human gastric cancer, as well as from porcine brain. In the present study, levels of alpha-1-6 FucT activity and mRNA expression have been determined during hepatocarcinogenesis in LEC rats which spontaneously develop hereditary hepatitis and hepatoma. The fetal liver contained the highest enzymatic activity, which tended to increase in inverse proportion to gestation. The enzymatic activity was significantly increased in hepatoma tissues as compared with uninvolved adjacent tissues. Northern-blot analysis revealed high expression of alpha-1-6 FucT mRNA in hepatoma tissues, whereas the expression was fairly low in normal, hepatitis and uninvolved adjacent liver tissues. While the fetal liver had the highest enzymatic activity, the expression of alpha-1-6 FucT mRNA was low, suggesting that another alpha-1-6 FucT is induced in fetal liver or that post-translational modification occurs. High expression of alpha-1-6 FucT was also observed in 3'-MeDAB-induced rat hepatomas and some rat hepatoma cell lines. Collectively, alpha-1-6 FucT was strongly enhanced from an early stage of hepatocarcinogenesis and was maintained at a high level in rat hepatomas.