INTERCELLULAR COMMUNICATION AND CANCER

细胞间通讯与癌症

• 批准号: 3163931
• 负责人: WERNER R LOEWENSTEIN
• 金额: $ 37.33万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-04-01 至 1992-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163931
• 关键词: autoradiography; calcium; calcium channel blockers; cell growth regulation; cell type; cellular oncology; cyclic AMP; diacylglycerols; electrical measurement; electron microscopy; electrophysiology; fluorescent dye /probe; freeze etching; genetic manipulation; genetic recombination; growth inhibitors; intercellular connection; liver cells; membrane permeability; neoplasm /cancer genetics; neoplastic growth; oncogenes; phosphatidylinositols; plasmids; temperature sensitive mutant; tissue /cell culture; viral carcinogenesis; virus genetics

The long-term objective of our research is to study the role of junctional cell-to-cell communication in growth control, in particular, the role of alterations in communication in the etiology of cancer. We will now examine the action on junctional communication of several viral oncogenes and cellular proto- oncogenes, in particular, v-src and c-src. We inquire into the mechanisms by the which these oncogenes downregulate communication. We focus on their action on the phosphoinositide messenger route, particularly its diacylglycerol branch exploring how this route controls communication and the role of intracellular Ca in this control. Furthermore, we will investigate the mechanism by which the growth of certain transformed cells is inhibited by junctional communication with normal cells. We test what transformed cell types are susceptible to inhibition, and analyze the kinetics of the inhibitory interaction and its relation to the cell cycle. The basic experiments are carried out on cell cultures; transformation is induced by viruses or recombinant oncogene DNAs. The main approaches involve probing of junctional membrane permeabilities with intracellular fluorescent tracers (fluorescent-labelled peptides and dyes), and microfluorimetric and microluminescence image-intensifier techniques for detection of changes in free Ca concentration, including local changes, inside the cells.

我们研究的长期目标是研究 在生长控制中的连接单元间通信， 特别是，变化在交流中的作用 癌症的病因。 现在我们将检查有关交界的行动 几种病毒癌基因和细胞原始的通讯 肿瘤基因，尤其是V-SRC和C-SRC。 我们询问 这些肿瘤基因下调的机制 沟通。 我们专注于他们对磷酸肌醇的作用 Messenger路线，尤其是其二酰基甘油分支 这条路线如何控制沟通和 该对照中的细胞内Ca。 此外，我们将调查 某些转化细胞生长的机制 与正常细胞的连接通信抑制。 我们 测试哪些转化的细胞类型容易受到抑制作用，并且 分析抑制作用及其关系的动力学 到细胞周期。 基本实验是在细胞上进行的 文化；转化是由病毒或重组诱导的 癌基因DNA。 主要方法涉及探测 连接膜渗透率，细胞内荧光 示踪剂（荧光标记的肽和染料），以及 微富集和微发光图像 - 图像增强剂 检测自由CA浓度变化的技术， 包括局部变化，内部。