Transforming genes of avian sarcoma viruses

描述(由申请人提供)：锚地独立生长、逃避 接触或细胞密度依赖的生长抑制。增强的迁移和 侵袭活性是体外培养细胞最重要的特性之一 转化的细胞。它们与癌症的特征密切相关。 体内的细胞。参与调控这些基因的分子信号通路 用禽肉瘤细胞研究了转化细胞的特性 UR2病毒，编码一种被称为ROS的截短受体酪氨酸激酶，以及 它的功能丧失突变体，以及新发现的ROS下游 名为Vav3的效应器。结果表明，PI3激酶和RhoGTP酶 信号通路在ROS和Vav诱导中起着重要作用 与锚定无关的生长，摆脱接触抑制和增强 运动性和侵犯性。这项建议的目标是进一步剖析和 确定P13激酶和RhoGTP酶的下游信号通路 它们在调节锚地独立生长、逃避 成纤维细胞和上皮细胞的接触抑制、运动和侵袭 细胞。此外，新的基因和途径对这些转化很重要 本课程将探索各种属性。 具体目标是： 1.阐明与锚定无关生长有关的分子信号 细胞的数量。 2.阐明调控细胞运动和侵袭的分子信号。 3.探索参与细胞运动调控的新基因和新蛋白 入侵。 4.阐明逃避接触抑制的分子基础 成长。 可诱导的ROS和Vav癌基因以及各种结构性激活和 P13激酶和Rho GTP酶信号分子的显性负性突变 将用于剖析转化的成纤维细胞中的信号通路 上皮细胞。微阵列和蛋白质组分析将在IN中使用 用于识别与逃避有关的新基因的体外细胞系统和动物模型 接触抑制和转移侵袭。

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.