High expression of α‐1‐6 fucosyltransferase during rat hepatocarcinogenesis

Abstract

␣-1-6 Fucosylated ␣-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-␤-D-glucosaminide ␣-1-6 fucosyltransferase (␣-1-6 FucT), is the key enzyme involved in ␣-1-6 fucosylation of AFP, when and how the expression of ␣-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 ␣-1-6 FucT from human gastric cancer, as well as from porcine brain. In the present study, levels of ␣-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 ␣-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 ␣-1-6 FucT mRNA was low, suggesting that another ␣-1-6 FucT is induced in fetal liver or that post-translational modification occurs. High expression of ␣-1-6 FucT was also observed in 3Ј-MeDABinduced rat hepatomas and some rat hepatoma cell lines. Collectively, ␣-1-6 FucT was strongly enhanced from an early stage of hepatocarcinogenesis and was maintained at a high level in rat hepatomas. Int.

Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation*

“…Similar to the case of PC3 and LNCaP cells, the expression of FUT8 is low in normal liver but increased in HCC (35,36). Secreted fucosylated proteins from prostate cancer tissues need to be studied, which could lead to the identification of specific glycosylated forms of glycoproteins as novel biomarkers.…”

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

“…15 Interestingly, a high level of expression of ␣1-6 FucT was consistently observed, even in precancer nodules including adenoma but not in their surrounding tissues. On the other hand, while the gene expression of glycosyltransferases III and V was enhanced in LEC rat livers during hepatocarcinogenesis, they were expressed in both tumor and uninvolved adjacent tissues.…”

“…14 When ␣1- 6 FucT expression was investigated in hepatocarcinogenesis of a rodent model, it was dramatically enhanced in precancerous nodules as well as in cancer lesions, suggesting that ␣1-6 FucT is a likely candidate for the early diagnosis of hepatoma in humans. 15 Although the activity of ␣1-6 FucT can be detected in serum, a determination of its levels in liver tissues is important, because ␣1-6 FucT is distributed in various organs at different levels 16 and the enzyme operates in the Golgi apparatus.…”

Optimisation of the Cellular Metabolism of Glycosylation for Recombinant Proteins Produced by Mammalian Cell Systems

“…Alpha 1,6 fucosyltransferase is a glycosyltransferase enzyme that catalyses the transfer of fucose from GDP-fucose to the Asn-linked GlcNAc residue (Voynow et al 1991;Noda et al 1998). The enzyme is a type II transmembrane protein, consisting of a short amino-terminal cytoplasmic tail, a transmembrane domain and a large intraluminal carboxyl-terminal catalytic region (Breton et al 1998).…”