REGULATION OF LYMPHOCYTE ACTIVATION AND PROLIFERATION

淋巴细胞激活和增殖的调节

• 批准号: 3939201
• 负责人: L M NECKERS
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3939201
• 关键词: DNA directed DNA polymerase; cell growth regulation; cyclic AMP; growth inhibitors; immunohematology; leukocyte activation /transformation; lymphoblast; lymphocyte; messenger RNA; oncogenes; tissue /cell culture; transferrin

All cells studied to date require transferrin for growth. We and others have shown that antibodies to the transferrin receptor block the growth of lymphoblastoid cell lines. In mitogen- stimulated lymphocytes, these antibodies block proliferation. We are studying the processes which regulate the appearance of these receptors in lymphocytes and lymphoblastoid cell lines, and the function of these receptors in cell growth and metabolism. We have demonstrated that G1 arrest occurs in both normal and malignant cells when transferrin receptors are blocked, even if cells are expressing high levels of growth factor receptor messenger RNA and c-myc and c-myb messenger RNA. Furthermore, either blockage of calcium channels or addition of cAMP to cells results in G1 arrest and loss of transferrin receptor mRNA. The effect of cAMP can be detected at the level of transcription. We have begun to study the role of nuclear proteins in the transition of T cells from G0 to S phase. In an initial study, a c- myc antisense oligomer completely blocked the appearance of c- myc protein in mitogen treated T cells, yet these cells went on to express IL-2 receptors, transferrin receptors and DNA polymerase alpha protein. Yet they failed to synthesize DNA. We plan to continue to use antisense constructs to various nuclear proteins to study their role(s) in cell growth and activation. Initially, we are examining the requirements for several nuclear proteins in DNA polymerase alpha activity. To date, we have determine that two such proteins, c-myc and Ki-67, are required for polymerase alpha activity in vitro.

迄今为止研究的所有细胞的生长都需要转铁蛋白。我们和