COOPERATIVE EFFECTS OF VIRAL AND CELLULAR ONCOGENES

正常细胞向完全恶性肿瘤的发展是一个多步骤的过程。 包括启动、推广和进展事件的过程。这个 被称为癌基因的一系列细胞基因的“激活”是 其中几个事件背后的分子基础。两个这样的癌基因，ras 和myc，在某些肿瘤细胞系中被激活，并可以协同作用 在培养中转化原代啮齿动物细胞。我们已经测试了RAS和 MYC协同诱导C3H10T1/2细胞转化 建立了胚胎来源的细胞系。MYC基因转染的C3H10T1/2细胞 不形成转化灶；转ras基因的C3H10T1/2细胞表现出 转化发生率低(80个病灶/Mug ras)。有趣的是， C3H10T1/2细胞可使病灶形成频率提高15倍 与ras和myc共转染。此外，基于以下方面的比较 软琼脂中的形态和生长速度表明ras-myc焦点是 与ras焦点有很大不同。拟议的研究将研究 Ras和myc癌基因产物作为单独的药物和 相互配合，转化C3H10T1/2细胞。 我们将建立(1)管理RAS转换的参数以及如何 当ras和myc合作导致明显的 不同表型，(2)myc蛋白在协同中的作用 事件以及myc表达的时机是否对该角色至关重要，以及 (3)参与协同作用的myc蛋白的结构域 以及这些结构域是否与控制 Myc蛋白的核定位、DNA结合特性 Myc蛋白或myc蛋白转化禽类细胞的能力。 从这次调查中获得的数据将构成未来的核心 旨在识别外源性和/或内源性细胞因子的研究 与ras和myc癌基因产物一起参与 导致体内肿瘤形成的事件。

The progression of a normal cell to a fully malignant tumor is a multistep process involving events of initiation, promotion and progression. The "activation" of a diverse of cellular genes, called oncogenes, is the molecular basis behind several of these events. Two such oncogenes, ras and myc, are activated in certain tumor cell lines and can cooperate to transform primary rodent cells in culture. We have tested whether ras and myc cooperate to cause the transformation of C3H10T1/2 cells, an established cell line of embryonic origin. Myc transfected C3H10T1/2 cells do not form transformed foci; C3H10T1/2 cells transfected with ras show a low incidence of transformation (80 foci/Mug ras). Interestingly, the frequency of focus formation can be increased 15 fold when C3H10T1/2 cells are co-transfected with ras and myc. In addition, comparisons based on morphology and on growth rates in soft agar reveal that ras-myc foci are dramatically different from ras foci. The proposed study will examine the contributions of the ras and myc oncogene products, as separate agents and in cooperation with each other, to the transformation of C3H10T1/2 cells. We will establish (1) the parameters governing ras transformation and how these parameters change when ras and myc cooperate to cause a distinctly different phenotype, (2) the role of the myc protein in the cooperation event and whether the timing of myc expression is critical to that role and (3) the structural domains of the myc protein involved in cooperation with gas and whether these overlap with the structural domains governing the nuclear localization of the myc protein, the DNA binding properties of the myc protein or the ability of the myc protein to transform avian cells. The data obtained from this investigation will form the core of future studies aimed at identifying exogenous and/or endogenous cellular factors that participate with the ras and myc oncogene products in the cascade of events leading to in vivo tumor formation.