GLYCOSYLTRANSFERASE ACTIVATION IN COLONIC ADENOCARCINOMA

糖脂代谢的急剧变化与 致癌性转化暗示了膜的特殊作用 糖脂在调节细胞生长和细胞识别中的作用。 这些变化产生肿瘤特异性膜抗原 其在诊断上是有用的，并作为潜在的靶点， 免疫疗法 虽然许多肿瘤的例子 抗原已被记录，但可用的信息不多 与生物合成的调节机制有关， 阻止这些碳水化合物结构在正常细胞中的表达， 细胞和组织，并被激活，以产生它们在联合 肿瘤发生 各种乳糖系列碳水化合物 抗原已经被描述存在于人腺癌中。 最近的证据表明，激活正常的 未表达的β 1导致3 N-乙酰葡糖胺转移酶 所需的乳糖系列链合成发生在结肠 上皮细胞，并导致这些抗原的积累。 本申请建议将这些观察结果扩展到 详细说明这种酶和其他相关酶活性的相互作用 通过合成各种末端结构， 发生在这些肿瘤中。 β 1导致3 N- 乙酰葡糖胺转移酶，其被激活 将被广泛研究。 这项活动将 特征在于腺癌细胞系，纯化以 来自可溶性来源如血清或牛奶的均匀性， 根据对酶的物理性质的研究，抗体将 这些抗体将用于研究 以分离编码该酶的cDNA克隆。 这然后将 导致研究基因表达的调节， 发育和肿瘤发生。 这些研究将提供有关 与肿瘤发生有关的生化变化 这引起了一系列重要的和潜在的有用的， 人肿瘤抗原、基于乳糖系列的碳水化合物抗原。

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.