COOPERATIVE EFFECTS OF VIRAL AND CELLULAR ONCOGENES

正常细胞发展为完全恶性肿瘤是一个多步骤的过程 涉及启动、提升和进展的过程。 的 一种叫做癌基因的多种细胞基因的“激活”， 这些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， 转化培养中的原代啮齿动物细胞。 我们已经测试了ras和 myc协同作用引起C3 H10 T1/2细胞转化， 建立胚胎来源的细胞系。 Myc基因转染的C3 H10 T1/2细胞 不形成转化灶;转染ras的C3 H10 T1/2细胞显示出 转化发生率低（80个病灶/Mug ras）。 有趣的是 当C3 H10 T1/2细胞被激活时， 用ras和myc共转染。 此外，比较基于 形态学和在软琼脂中的生长速率显示ras-myc病灶是 与RAS灶有显著不同。 拟议的研究将审查 ras和myc癌基因产物作为单独的因子的贡献， 协同作用转化C3 H10 T1/2细胞。 我们将建立（1）控制ras变换的参数以及如何 当ras和myc协同作用时，这些参数改变， 不同表型;（2）myc蛋白在协同作用中的作用 事件以及myc表达的时间是否对该作用至关重要， (3)myc蛋白的结构域参与与 气体，以及这些是否与控制的结构域重叠 myc蛋白的核定位， 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成为未来研究的核心。 旨在鉴定外源和/或内源细胞因子的研究 参与ras和myc癌基因产物的级联反应， 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.