Transforming genes of avian sarcoma viruses

转化禽肉瘤病毒基因

• 批准号: 6471365
• 负责人: LU-HAI WANG
• 金额: $ 35.79万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-02-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6471365
• 关键词: athymic mouse; avian sarcoma virus; biological signal transduction; cadherins; cell motility; contact inhibition; epithelium; fibroblasts; gene mutation; guanosinetriphosphatases; microarray technology; neoplastic transformation; oncogenes; phosphatidylinositol 3 kinase; tissue /cell culture; viral carcinogenesis; virus genetics

DESCRIPTION (provided by applicant): Anchorage-independent growth, evasion of contact or cell density-dependent inhibition of growth. Enhanced migration and invasion activities are among the most important properties of in vitro transformed cells. They correlate closely with the characteristics of cancer cells in vivo. The molecular signaling pathways involved in regulating these properties of transformed cells have been investigated by using avian sarcoma virus UR2, which encodes a truncated receptor tyrosine kinase called Ros, and its loss-of-function mutants, as well as a newly discovered Ros down stream effector called Vav3. The results indicate that PI3 kinase and the RhoGTPase signaling pathways play an important role in Ros- and Vav-induced anchorage-independent growth, escape from contact inhibition and enhancment of motility and invasion. The objective of this proposal is to further dissect and identify the down stream signaling pathways of P13 kinase and the RhoGTPases which are important in regulating anchorage-independent growth, evasion of contact inhibition, and motility and invasion of fibroblasts and epithelial cells. In addition, novel genes and pathways important for these transforming properties will be explored. The specific aims are: 1. To elucidate molecular signaling important for anchorage independent growth of cells. 2. To elucidate molecular signaling regulating cell motility and invasion. 3. To explore novel genes and proteins involved in regulating cell motility and invasion. 4. To elucidate the molecular basis for evasion of contact inhibition of growth. Inducible Ros and Vav oncogenes along with various constitutively activated and dominant negative mutants of P13 kinase and Rho GTPases signaling molecules will be used to dissect signaling pathways in transformed fibroblasts and epithelial cells. Microarray and proteomic analysis will be used in the in vitro cell system and animal models to identify novel genes involved in evasion of contact inhibition and metastatic invasion.

描述（由申请人提供）： 不依赖锚定的生长，逃避 接触或细胞密度依赖性生长抑制。增强的迁移和 侵袭活性是体外最重要的特性之一 转化的细胞。它们与癌症的特征密切相关 体内的细胞。参与调节这些的分子信号通路 使用禽肉瘤研究了转化细胞的特性 病毒 UR2，编码一种称为 Ros 的截短受体酪氨酸激酶，以及 其功能丧失突变体，以及下游新发现的 Ros 效应器称为 Vav3。结果表明 PI3 激酶和 RhoGTPase 信号通路在 Ros 和 Vav 诱导的过程中起重要作用 不依赖锚定的生长，摆脱接触抑制并增强 运动性和侵袭性。该提案的目的是进一步剖析和 识别 P13 激酶和 RhoGTPase 的下游信号传导通路 这对于调节锚定独立生长、逃避 接触抑制以及成纤维细胞和上皮细胞的运动和侵袭 细胞。此外，新的基因和途径对于这些转化很重要 将探索属性。 具体目标是： 1. 阐明对于锚定独立生长重要的分子信号传导 细胞。 2. 阐明调节细胞运动和侵袭的分子信号传导。 3. 探索参与调节细胞运动的新基因和蛋白质 入侵。 4. 阐明逃避接触抑制的分子基础 生长。 诱导型 Ros 和 Vav 癌基因以及各种组成型激活和 P13 激酶和 Rho GTPases 信号分子的显性失活突变体 将用于剖析转化成纤维细胞中的信号传导途径和 上皮细胞。微阵列和蛋白质组分析将用于 体外细胞系统和动物模型来识别参与逃避的新基因 接触抑制和转移侵袭。