Gene expression of α1-6 fucosyltransferase in human hepatoma tissues:: A possible implication for increased fucosylation of α-fetoprotein
Gene expression of α1-6 fucosyltransferase in human hepatoma tissues:: A possible implication for increased fucosylation of α-fetoprotein
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DOI：
10.1002/hep.510280408
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发表时间：
1998-10-01
期刊：
影响因子：
13.5
通讯作者：
Taniguchi, N
中科院分区：
文献类型：
--
作者：
Noda, K;Miyoshi, E;Taniguchi, N
肝癌患者血清中的α 1-6岩藻糖基化甲胎蛋白（AFP）已被用于肝癌与慢性肝病的鉴别诊断。然而，这种改变发生的分子机制在很大程度上仍然未知。为了解决这个问题，我们纯化了GDP-L-Fuc：N-乙酰基-β-D-氨基葡萄糖苷α 1-6岩藻糖基转移酶（α 1-6 FucT），一种参与猪脑以及人胃癌细胞系中N-聚糖α 1-6岩藻糖基化的酶，并克隆了它们的基因。本研究检测了12例人肝癌组织中α 1-6 FucT mRNA的表达水平和该酶的活性，并与癌旁组织和正常肝脏进行了比较。α 1-6 FucT活性的平均+/- SD在正常对照肝脏中为78 +/- 41 pmol/h/mg，在邻近未受累肝组织中为202 +/- 127 pmol/h/mg（慢性肝炎：181 +/- 106 pmol/h/mg;肝硬化：233 +/- 164 pmol/h/mg），在HCC组织中为194 +/- 72 pmol/h/mg。除少数病例外，α 1-6 FucT的mRNA表达也与酶活性成比例地增强，表明α 1-6 FucT表达在慢性肝病，特别是肝硬化中增加。将α 1-6 FucT基因转染到培养的大鼠肝细胞中显著增加了α 1-6 FucT活性，并导致细胞裂解物和条件培养基中透镜culinaris凝集素（LCA）结合蛋白的增加。当α 1-6 FucT基因转染到最初显示低水平α 1-6 FucT表达的人HCC细胞系Hep 3B中时，α 1-6-岩藻糖基化AFP在条件培养基中显著增加。总的来说，这些结果表明α 1-6 FucT表达的增强增加了几种蛋白质的岩藻糖基化，包括AFP，HCC患者的α 1-6-岩藻糖基化AFP水平部分由α 1-6 FucT基因表达上调引起。
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.