NCI CLINICAL INVESTIGATOR AWARD PROGRAM

血小板衍生生长因子（PDGF）控制培养物的生长 来自多种脊索动物物种的结缔组织细胞。 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-3T3 成纤维细胞的生长需要 PDGF，并且在受到 PDGF 刺激后， 选择性合成mRNA和蛋白质家族，其积累 似乎是 DNA 合成和细胞复制所必需的。 各种 转化的 3T3 细胞衍生物不需要 PDGF 生长，并且 组成型合成 PDGF 调节的 mRNA 和蛋白质。 虽然 已知人类成纤维细胞对 PDGF 产生有丝分裂反应， PDGF调节人成纤维细胞和外植人的蛋白质合成 结缔组织肿瘤（肉瘤）细胞。 我将证明 PDGF 尚未研究在人体细胞中启动特定蛋白质合成， 不具备人类结缔组织肿瘤的PDGF生长要求。 在这个项目中，我将定义正常人的 PDGF 生长要求 成纤维细胞，并且这些 PDGF 调节的蛋白质是组成型的 由那些不依赖于PDGF的外植肉瘤细胞合成 为了成长。 肿瘤外植体中 c-sis mRNA 的表达将 通过 Northern 凝胶和斑点杂交分析进行评估，并将 被证明存在于一些但不是全部 PDGF 独立肿瘤中 外植体。 这项工作将建立 PDGF 损失之间的关系 肉瘤细胞的生长调节、c-sis 和组成型表达 PDGF 调节蛋白的合成，从而揭示其机制 正常和恶性细胞生长。

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.