GLYCOSYLATION IN EXPERIMENTAL LIVER CARCINOGENESIS

本研究的长期目标是揭示 糖蛋白的糖基化在致癌过程中的作用。 的 工艺提案源于最近的发现， 结节的大鼠开始与肝癌和促进 与乳清酸表达一种新的糖基转移酶，N-乙酰 葡糖胺转移酶III（GnT III）参与合成 N-连接的N-乙酰葡糖胺 细胞糖蛋白的寡糖。 的意义 这一观察结果在于，在肝组织中， 结构仅在肝细胞癌中检测到， 在正常肝细胞糖蛋白中。 实验旨在确定在什么阶段， 新的酶被诱导， 诱导的酶在整个过程中持续存在。 为此 目的大鼠将用肝脏致癌物启动， 用乳清酸促进。 老鼠将在不同的时间被杀死 之后，将监测肝结节和癌症， GnT III的存在。 该酶也将被纯化， 制备结节和抗体。 使用抗体和 免疫组化方法早期显微镜下推定 包括原发性肝囊肿在内的癌前病变将 监测GnT III的存在。 本研究的意义在于癌症相关糖基化 新的糖基转移酶的模式和诱导已经被 研究主要集中在坦率的癌和其他恶性病变 本研究首次探讨了这些问题 在整个过程中系统地处理重要问题 致癌过程 从这个产生的信息 研究我们将更好地评估的意义， 糖基转移酶在致癌过程中，以及在 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.