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SURFACE MEMBRANES OF NORMAL AND CANCER CELLS

正常细胞和癌细胞的表面膜

基本信息

批准号：
3165105
负责人：
LEONARD WARREN
金额：
$ 19.05万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-12-01 至 1992-02-29
项目状态：
已结题

项目摘要

It has been found that incubation of UDP-galactose with GTP, Mn ions and extracts of transformed cells results in the formation of several rapidly migrating products. Two of these products are dominant, "Fast Peak 2" (FP2) and "Fast Peak 4" (FP4). The reaction is catalyzed by extracts of transformed cells with mutated or elevated levels of ras oncogene product (K-ras, H-ras and N-ras). Activity is also seen in human tumor cell lines (breast, lung, bladder), SV40-transformed cells and chemically transformed liver cells. The reaction is not detected in a variety of control cells, polyoma and Rous virus-transformed cells and some malignant cells. Preliminary experiments indicate that the reaction catalyzed by an extract of KMSV-transformed mouse fibroblasts can be inhibited by an anti-ras monoclonal antibody. Our aim is to: (a) obtain sufficient material to establish the structures of FP2 and FP4; (b) study their effects on cells and reactions related to growth control in order to establish their role in malignant (and normal) cells, i.e., whether the FP derivatives are involved in normal control of growth and differentiation; (c) fractionate the enzymes and factors involved in the synthesis of FP; (d) determine the nature of the reaction and the metabolic relation of FP2 and FP4; (e) establish that the ras gene product is a part of the mechanism and determine the action of the ras protein in normal and malignant cells; and (f) determine the distribution of the FP synthesizing enzymes in control and malignant tissues. We also plan to complete our studies in progress on: 1) the degradation of CMPNAN to form a putative CMPpyruvate. 2) comparison of glycopeptides of control and transformed cells. 3) the influence of environment and drugs on the carbohydrate component of IgG produced by hybridomas and the consequences of altered carbohydrate structure.

已发现UDP-半乳糖与GTP、Mn离子和转化细胞的提取物导致几种快速的迁移产品。其中两款产品占据主导地位，“快峰2” (FP2)快速峰值4（Fast Peak 4）该反应是催化的提取物， ras癌基因产物水平突变或升高的转化细胞（K-ras、H-ras和N-ras）。活性也见于人类肿瘤细胞系（乳腺、肺、膀胱）、SV 40转化细胞和化学转化细胞肝细胞在多种对照细胞中未检测到该反应，多瘤和Rous病毒转化的细胞和一些恶性细胞。初步实验表明，由提取物催化的反应的KMSV转化小鼠成纤维细胞可以被抗ras 单克隆抗体我们的目标是：（a）获得足够的材料，（B）研究它们对细胞的作用和与生长控制，以确定其在恶性（和正常）细胞，即，FP衍生物是否参与正常控制生长和分化;（c）分解酶和因子参与FP的合成;（d）确定反应的性质以及FP 2和FP 4的代谢关系;（e）确定ras基因产品是机制的一部分，并决定ras的作用蛋白质在正常和恶性细胞中的分布;和（f）确定 FP合成酶在正常组织和恶性组织中的表达。我们也计划完成我们正在进行的以下研究： 1)CMPNAN降解形成推定的CMP丙酮酸。 2)对照和转化细胞的糖肽的比较。 3)环境和药物对糖组成的影响杂交瘤产生的IgG和碳水化合物改变的后果结构