Noda K, Miyoshi E, Uozumi N, Gao C X, Suzuki K, Hayashi N, Hori M, Taniguchi N
Department of Biochemistry, Osaka University Medical School, Suita, Japan.
Int J Cancer. 1998 Jan 30;75(3):444-50. doi: 10.1002/(sici)1097-0215(19980130)75:3<444::aid-ijc19>3.0.co;2-8.
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.
α-1-6岩藻糖基化甲胎蛋白（AFP）在原发性肝癌患者中升高，有人认为它可作为肝癌预后不良的早期指标和预测因子。尽管GDP-L-岩藻糖基-N-乙酰-β-D-葡糖胺α-1-6岩藻糖基转移酶（α-1-6 FucT）是参与AFP α-1-6岩藻糖基化的关键酶，但在肝癌发生过程中α-1-6 FucT的表达何时以及如何增强尚不清楚。最近，我们建立了一种针对该酶的简便检测方法，并成功从人胃癌以及猪脑中纯化和克隆了α-1-6 FucT的cDNA。在本研究中，测定了自发发生遗传性肝炎和肝癌的LEC大鼠肝癌发生过程中α-1-6 FucT活性和mRNA表达水平。胎肝中的酶活性最高，且与妊娠呈反比关系，有升高趋势。与未受累的相邻组织相比，肝癌组织中的酶活性显著增加。Northern印迹分析显示，α-1-6 FucT mRNA在肝癌组织中高表达，而在正常、肝炎和未受累的相邻肝组织中表达很低。虽然胎肝中的酶活性最高，但α-1-6 FucT mRNA的表达却很低，这表明胎肝中诱导了另一种α-1-6 FucT，或者发生了翻译后修饰。在3'-甲基二乙基亚硝胺诱导的大鼠肝癌和一些大鼠肝癌细胞系中也观察到α-1-6 FucT的高表达。总体而言，α-1-6 FucT在肝癌发生的早期就强烈增强，并在大鼠肝癌中维持在高水平。
