GLYCOSYLATION IN EXPERIMENTAL LIVER CARCINOGENESIS

这项研究的长期目标是揭示 糖蛋白在致癌过程中的糖基化。这个 工艺建议源于最近发现的肝脏 一种致癌剂诱发和促进的大鼠结节 用冬凌草酸表达一种新的糖基转移酶N-乙酰 氨基葡萄糖基转移酶III(GnT III)参与合成 对分N-链中N-乙酰氨基葡萄糖残基 细胞糖蛋白的低聚糖。的重要意义。 这一观察结果在于这样一个事实：在肝组织中， 结构只在肝细胞癌中检测到，而不是 正常肝细胞中的糖蛋白。 已经设计了实验来确定在什么阶段 肝癌的发生是由新的酶诱导的，是否 诱导的酶在整个过程中持续存在。为了这个 目的大鼠将用一种肝致癌物质和 用奥罗里酸促进。老鼠会在不同的时间被扑杀 之后，将监测肝脏结节和癌症 GnT III的存在。该酶也将从 制备结节和抗体。使用抗体和 免疫组织化学方法早期镜检推定 癌前病变包括启动的肝囊肿将是 监测GnT III的存在。 本研究的意义在于癌相关糖基化 新的糖基转移酶的模式和诱导 主要研究对象为直肠癌和其他恶性病变。 而本研究则是此类研究中的第一个。 以系统的方式在整个过程中的重要方面 致癌过程。利用由此生成的信息 我们将在研究中更好地评估 糖基转移酶在致癌过程中的作用 人类癌症的诊断和预后。

The long term objective of this study is to uncover the relevance of glycosylation of glycoproteins in carcinogenic process. The process proposal stems from recent discovery that the hepatic nodules of rats initiated with a hepatocarcinogen and promoted with orotic acid expressed a novel glycosyl transferase, N-acetyl glucosaminyltransfease III (GnT III) involved in the synthesis of bisecting N-acetylglucosamine residue in N-linked oligosaccharides of cellular glycoproteins. The significance of this observation lies in the fact that in liver tissue the bisecting structures are detected only in hepatocellular carcinoma and not in the normal liver cell glycoproteins. Experiments have been designed to ascertain at what stage during hepatocarcinogenesis the novel enzyme is induced and whether the induced enzyme persists throughout the process. For this purpose rats will be initiated with a liver carcinogen and promoted with orotic acid. Rats will be killed at various times afterwards and the liver nodules and cancers will be monitored for the presence of GnT III. The enzyme will also be purified from the nodules and antibody prepared. Using the antibody and immunohistochemical methods early microscopic putative preneoplastic lesions including initiated hepatocystes will be monitored for the presence of GnT III. The significance of this study is that cancer related glycosylation patterns and induction of new glycosyl transferases have been studied mostly in frank carcinomas and other malignant lesions and the present study is first of its kind to probe into these important aspects in systematic manner during the entire carcinogenic process. With the information generated from this study we will in a better position to assess the significance of glycosyl transferases in the carcinogenic process as well as in the diagnosis and prognosis of cancer in human.