GLYCOSYLTRANSFERASE ACTIVATION IN COLONIC ADENOCARCINOMA

糖脂代谢的戏剧性变化与 致癌转化涉及膜的特定作用 糖脂在调节细胞生长和细胞识别中的作用。 这些变化导致肿瘤特异性膜抗原的产生。 它们在诊断上是有用的，并且可以作为潜在的目标 免疫疗法。尽管这些肿瘤的许多例子 抗原已经被记录在案，但可用的信息不多 与生物合成的调节机制有关的 阻止这些碳水化合物结构在正常人群中表达 细胞和组织，并被激活以联合产生它们 与肿瘤的发生有关。各种基于乳糖系列的碳水化合物 抗原已被描述为存在于人类腺癌中。 最近的证据表明，正常情况下一种 未表达的β1导致3N-乙酰氨基葡萄糖基转移酶 内酯系列链合成所需的物质存在于结肠中 上皮细胞，并导致这些抗原的积累。 此应用程序建议将这些观察扩展到在 该酶和其他相关酶活性的详细相互作用 随着各种末级结构的合成， 发生在这些肿瘤中。Beta 1通向3N- 联合激活的乙酰氨基葡萄糖基转移酶 对其致癌作用将进行广泛的研究。这项活动将是 以腺癌细胞株为特征，纯化到 来自可溶来源的同质性，如血清或牛奶，这 研究了酶的物理性质，抗体将 为它做好准备，这些抗体将用于研究 分离编码该酶的cDNA克隆。然后，这将是 导致了对这两个过程中基因表达调控的研究 发育和肿瘤发生。 这些研究将提供更多关于 与肿瘤发生相关的生化变化 这导致了一系列重要的和潜在有用的 人类肿瘤抗原，以乳糖为基础的碳水化合物抗原。

Dramatic changes in glycolipid metabolism associated with oncogenic transformation implicate a specific role for membrane glycolipids in regulation of cell growth and cellular recognition. These changes give rise to tumor specific membrane antigens which are useful diagnostically and as potential targets for immunotherapy. Although many examples of these tumor antigens have been documented, not much information is available relating to the mechanism of regulation of biosynthesis which prevents expression of these carbohydrate structures in normal cells and tissues and is activated to produce them in association with oncogenesis. A variety of lacto-series based carbohydrate antigens have been described to occur in human adenocarcinomas. Recent evidence has shown that activation of a normally unexpressed beta 1 leads to 3N-acetyl-glucosaminyltransferase required for lacto-series chain synthesis occurs in colonic epithelial cells and results in accumulation of these antigens. This application proposes to extend these observations to study in detail interactions of this and other enzyme activities associated with the synthesis of a variety of end-stage structures which occur in these tumors. The beta 1 leads to 3N- acetylglucosaminyltransferase which is activated in association with oncogenesis will be extensively studied. This activity will be characterized in adenocarcinoma cell lines, purified to homogeneity from a soluble source such as serum or milk and this enzyme studied in terms of its physical properties, antibodies will be prepared against it and these antibodies will be used in studies to isolate cDNA clones which encode the enzyme. This will then lead to studies of the regulation of gene expression during both development and oncogenesis. These studies will provide further information relating to the biochemical changes occurring in association with oncogenesis which gives rise to an important and potentially useful series of human tumor antigens, lacto-series based carbohydrate antigens.