Characterization of Ras-driven human epidermal neoplasia

Ras 驱动的人表皮瘤形成的特征

• 批准号: 33464224
• 负责人: Dr. Markus Kretz
• 金额: --
• 依托单位: Lehrstuhl für Biochemie I
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/33464224?language=en
• 关键词: Characterization; Ras; driven; human; epidermal

Epidermal squamous cell carcinoma (SCC) represents one of the two most abundant cancers in the USA. Ras is supposed to play a major role in the development of murine and human SCC. Induction of Ras and CDK4 could be demonstrated in a subset of human SCC s. Furthermore, co-expression of Ras with CDK4 led to the induction of invasive human epidermal neoplasia indistinguishable from SCC at all stages analyzed but the underlying mechanistic basis is largely unknown. This research fellowship would enable me to study the functional role of Ras and its related components in the development of human epidermal tumorigenesis which I would like to analyze according to the following research concept: I plan to characterize the influence of three Ras effectors named Raf, PI3K and RalGEF as well as the corresponding signal transduction pathways which are known to influence cell proliferation, de-differentiation, migration or angiogenesis during tumor development. Ras mutants designed to selectively activate or inactivate one of these pathways and their effectors themselves will be used to analyze the impact of each of these pathways to Ras-driven human neoplasia. With this research concept I hope to illuminate the functional relevance of those Ras effector pathways and their extend of necessity or sufficiency for initiation of human epidermal neoplasia. The work on Ras-driven human epidermal neoplasia will expand my knowledge about the mechanistic basis of tumor development and its influence on skin homeostasis. It will help me to establish my own laboratory working on epidermal tumorigenesis when I return to Germany.

表皮鳞状细胞癌（SCC）是美国最常见的两种癌症之一。Ras被认为在小鼠和人SCC的发展中起主要作用。Ras和CDK4的诱导可以在人类SCC的一个子集中得到证实。此外，Ras与CDK4的共表达导致在分析的所有阶段均无法与SCC区分的侵袭性人表皮瘤形成的诱导，但其潜在的机制基础在很大程度上是未知的。这项研究奖学金将使我能够研究Ras及其相关成分在人类表皮肿瘤发生发展中的功能作用，我想根据以下研究概念进行分析：我计划表征三种Ras效应物Raf、PI3K和RalGEF的影响以及已知影响细胞增殖、去分化、在肿瘤发展过程中的迁移或血管生成。Ras突变体被设计为选择性地激活或抑制这些途径之一及其效应物本身，将用于分析这些途径中的每一个对Ras驱动的人类肿瘤的影响。有了这个研究概念，我希望阐明这些Ras效应通路的功能相关性和它们的必要性或充分性的范围内启动人类表皮肿瘤。Ras驱动的人类表皮肿瘤的工作将扩大我对肿瘤发展的机制基础及其对皮肤稳态的影响的知识。当我回到德国时，它将帮助我建立自己的实验室，研究表皮肿瘤的发生。