NCI CLINICAL INVESTIGATOR AWARD PROGRAM

NCI 临床研究者奖励计划

• 批准号: 3079500
• 负责人: RICHARD B WOMER
• 金额: $ 5.83万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 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/3079500
• 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

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)对培养细胞生长的调控作用 来自各种脊索动物的结缔组织细胞。至少是这样的 猴转化癌基因(v-sis)部分编码 肉瘤病毒及其细胞同源物c-sis。小鼠BALB/c-3T3 成纤维细胞生长需要PDGF，在PDGF刺激下， 选择性地合成一组mRNAs和蛋白质，其积累 似乎是DNA合成和细胞复制所必需的。五花八门 转化的3T3细胞衍生物不需要PDGF来生长，并且 结构性合成PDGF调控的mRNAs和蛋白质。尽管 已知人成纤维细胞对PDGF有丝分裂反应， PDGF对人成纤维细胞和移植人蛋白质合成的调控 结缔组织肿瘤(肉瘤)细胞。我将证明PDGF 在人类细胞中启动特定的蛋白质合成还没有研究过， 不具备人结缔组织肿瘤对PDGF生长的要求。 在这个项目中，我将定义正常人对PDGF的生长需求 成纤维细胞，这些受PDGF调节的蛋白是结构性的 由移植的不依赖PDGF的肉瘤细胞合成 为了增长。C-sis基因在肿瘤外植体中的表达 进行Northern凝胶和斑点杂交分析，并将 被证明存在于部分但不是全部的非PDGF非依赖性肿瘤中 外植体。这项工作将建立PDGF丢失之间的关系 肉瘤细胞生长调控、c-sis和组成型蛋白的表达 PDGF调节蛋白的合成，从而阐明其作用机制 正常和恶性细胞生长。