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NCI CLINICAL INVESTIGATOR AWARD PROGRAM

NCI 临床研究者奖励计划

基本信息

批准号：
3079501
负责人：
RICHARD B WOMER
金额：
$ 6.12万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-05-01 至 1988-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3079501
关键词：
cell growth regulation connective tissue neoplasm fibroblasts fibrosarcoma gene expression genetic manipulation glioma human tissue messenger RNA neoplasm /cancer genetics neoplasm /cancer transplantation neoplastic cell oncogenes osteosarcoma platelet derived growth factor rhabdomyosarcoma sarcoma tissue /cell culture

项目摘要

The platelet-derived growth factor (PDGF) controls the growth of cultured connective tissue cells from a variety of chordate species. It is at least partially encoded by the transforming oncogene (v-sis) of the simian sarcoma virus, and its cellular homologue c-sis. Mouse BALB/c-3T3 fibroblasts require PDGF for growth, and upon stimulation with PDGF, selectively synthesize a family of mRNAs and proteins, whose accumulation appears to be necessary for DNA synthesis and cell replication. Various transformed 3T3 cell derivatives do not require PDGF for growth, and constitutively synthesize the PDGF-modulated mRNAs and proteines. Though human fibroblasts are known to respond mitogenically to PDGF, PDGF-modulated protein synthesis in human fibroblasts and explanted human connective tissue tumor (sarcoma) cells. I will demonstrate that PDGF initiates specific protein synthesis in human cells has not been studied, not have the PDGF growth requirements of human connective tissue tumors. In this project I will define the PDGF growth requirements of normal human fibroblasts, and that these PDGF-modulated proteins are constitutively synthesized by those explanted sarcoma cells which are independent of PDGF for growth. Expression of c-sis mRNA in the tumor explants will be evaluated with Northern gel and dot-blot hybridization analysis, and will be shown to be present in some, but not all, of the PDGF-independent tumor explants. This work will establish the relationships between loss of PDGF growth regulation in sarcoma cells, expression of c-sis and constitutive synthesis of PDGF-modulated proteins, and thus shed light on mechanisms of normal and malignant cell growth.

血小板衍生生长因子（PDGF）控制培养的来自各种脊索动物物种的结缔组织细胞。它至少是部分由猿猴的转化癌基因（v-sis）编码肉瘤病毒及其细胞同源物c-sis。小鼠BALB/c-3 T3 成纤维细胞需要PDGF来生长，并且在用PDGF刺激时，选择性地合成一个家族的mRNA和蛋白质，似乎是DNA合成和细胞复制所必需的。各种转化的3 T3细胞衍生物生长不需要PDGF，组成型合成PDGF调节的mRNA和蛋白质。虽然已知人成纤维细胞对PDGF有丝分裂反应，人成纤维细胞和正常人中PDGF调节的蛋白质合成结缔组织肿瘤（肉瘤）细胞。我将证明PDGF 在人类细胞中启动特异性蛋白质合成的研究还没有进行，不具有人结缔组织肿瘤的PDGF生长要求。在这个项目中，我将定义正常人的PDGF生长需求，成纤维细胞，并且这些PDGF调节的蛋白质是组成性的，由那些不依赖PDGF的恶性肉瘤细胞合成促进增长。 c-sis mRNA在肿瘤组织块中的表达将是用北方凝胶和斑点杂交分析进行评价，显示存在于一些但不是全部的PDGF非依赖性肿瘤中，外植体这项工作将建立PDGF的损失之间的关系肉瘤细胞的生长调节，c-sis的表达和组成性 PDGF调节蛋白的合成，从而阐明了正常和恶性细胞生长。