NCI CLINICAL INVESTIGATOR AWARD PROGRAM

点击翻译按钮获取中文摘要

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.