Barrière C, Marjou F El, Louvard D, Robine S
CNRS-Institut Curie, Equipe de morphogenèse et de signalisations cellulaires, 26, rue d'Ulm, 75248 Paris, France.
Bull Cancer. 2009 Dec;96 Suppl:S5-14. doi: 10.1684/bdc.2009.0992.
Activating mutations of the oncogene K-ras are found in one third of all human cancers. Much of our knowledge on K-ras signal transduction and its influence on tumor initiation and progression come from in vitro studies with cell lines. However, mouse models of human cancer allow a much more faithful recapitulation of the human disease, and the in vivo perspective is crucial for our understanding of neoplasia. In recent years, several new murine models for K-ras-induced tumorigenesis have been described. They allow new insights into the specific role that oncogenic K-ras proteins play in different solid tumors, and they permit the molecular dissection of the pathways that are initiated by somatic mutations in subsets of cells. Key advances have been made by the use of tissue-specific and inducible control of expression, which is achieved by the Cre/loxP technology or the tetracycline system. From these sophisticated models, a common picture emerges: the effects of K-ras on tumor initiation depend strongly on the cellular context, and different tissues vary in their susceptibility to K-ras transformation.
在所有人类癌症中，三分之一存在致癌基因K-ras的激活突变。我们对K-ras信号转导及其对肿瘤起始和进展影响的许多了解都来自对细胞系的体外研究。然而，人类癌症的小鼠模型能更真实地重现人类疾病，且体内视角对于我们理解肿瘤形成至关重要。近年来，已描述了几种用于K-ras诱导肿瘤发生的新型小鼠模型。它们使我们对致癌K-ras蛋白在不同实体瘤中所起的特定作用有了新的认识，并且允许对由细胞亚群中的体细胞突变引发的信号通路进行分子剖析。通过使用Cre/loxP技术或四环素系统实现的组织特异性和诱导性表达控制取得了关键进展。从这些复杂的模型中，呈现出一个共同的情况：K-ras对肿瘤起始的影响在很大程度上取决于细胞背景，并且不同组织对K-ras转化的敏感性各不相同。
