HEPATIC AND COLONIC SIALYLTRANSFERASE EXPRESSION

细胞唾液酸组分的顺序修饰 黏附分子和其他糖蛋白是通过 正常的细胞分化会继续进行。红豆杉的唾液酸寡糖 异常的糖蛋白也参与了糖尿病的病理生理学。 各种疾病，包括转移性结直肠癌。双环芳香烃的合成 每个唾液酸基连接由特定的唾液酸基转移酶催化，并且 因此，这些酶活性的波动可能会起到 在分化等基本生物过程中的关键作用 和转移行为。向最终理解 不同唾液酸基转移酶表达的协调机制 在正常和病变组织中，这种应用的目的是： 人唾液酸基转移酶基因在真核细胞中的表达 描绘由不同的编码序列催化的唾液酸键 蛋白质；对人唾液酸基转移酶mRNAs进行组织研究； 比较一组唾液酸基转移酶的mRNA表达和酶活性 人类癌细胞系；并在同一组细胞系中进行研究 可能影响人体健康水平的药物的监管效果 唾液酸转移酶的表达。中国仓鼠卵巢细胞将被 重组唾液酸基转移酶基因在载体中的表达 向量。表达的唾液酸基转移酶的活性将是 其特征是其受体底物的测定和对其的分析 合成的低聚糖。组织调查将是 通过Northern杂交在人类手术标本中进行 分析和S1保护检测。癌细胞小组将包括 地塞米松、正丁酸、维甲酸和甲状腺激素。结果是 将构成理解决定因素的基础 唾液酸基转移酶的活性及其生物学研究展望 唾液酸化作用。

Sequential modification of the sialic acid component of cell adhesion molecules and other glycoproteins is one of the mechanisms by which normal cell differentiation proceeds. The sialyl oligosaccharides of aberrant glycoproteins have also been implicated in the pathophysiology of various diseases, including metastatic colorectal cancer. The synthesis of each sialyl linkage is catalyzed by a specific sialyltransferase and fluctuations in the activities of these enzymes may therefore play a critical role in such fundamental biological processes as differentiation and metastatic behavior. Towards an eventual understanding of the mechanisms that coordinate expression of the different sialyltransferases in normal and diseased tissues, objectives of this application are: to express cDNAs for human sialyltransferases in eucaryotic cells and delineate the sialyl linkages that are catalyzed by the different encoded proteins; to perform a tissue survey of human sialyltransferase mRNAs; to compare sialyltransferase mRNA expression and enzyme activity in a panel of human cancer cell lines; and to investigate in the same panel of cell lines the regulatory effects of agents that are likely to influence levels of sialyltransferase expression. Chinese hamster ovary cells will be transfected with constructs of the sialyltransferase cDNAs in plasmid vectors. The activities of expressed sialyltransferases will be characterized by determination of their acceptor substrates and analysis of the oligosaccharides that are synthesized. The tissues survey will be conducted in human surgical specimens through Northern hybridization analysis and S1 protection assays. The panel of cancer cells will include dexamethasone, n-butyrate, retinoic acid and thyroid hormone. The results will form the basis for an understanding of the determinants of the activities of sialyltransferases and future studies of the biological functions of sialylation.