Mougneau E, Cerni C, Tillier F, Cuzin F
Unité INSERM 273, Université de Nice, France.
Oncogene Res. 1988;2(2):177-88.
Early passage FR3T3 rat cells were co-transfected with a neo resistance gene and pSVc-myc-1, an SV40-driven expression vector carrying an activated murine myc oncogene. Selection in G418 medium produced clones expressing the exogenous myc gene at various levels, with a concomitant loss of expression of the normal c-myc allele. These clones were phenotypically normal, but, in fluctuation tests performed according to Luria and Delbrück (1943) on subcultures independently derived from the same clone, transformed foci appeared as stochastic events with a wide range of fluctuation. These results indicate that expression of the oncogene was not sufficient to induce the appearance of transformed growth properties, and that secondary genetic changes are required, most likely mutations in cellular proto-oncogenes. Within a single clone, independent transformants exhibited different tumorigenic potentials, spanning from high efficiency to no detectable tumor induction, without any clear correlation with their degree of in vitro transformation. Tumors and cell lines established from independent tumors, while maintaining the exogenous myc gene without gross rearrangement of its structure, no longer expressed the oncogene and resumed the expression of the normal allele.
早期传代的FR3T3大鼠细胞与新霉素抗性基因和pSVc-myc-1共转染，pSVc-myc-1是一种携带活化鼠myc癌基因的SV40驱动的表达载体。在G418培养基中进行筛选产生了在不同水平表达外源myc基因的克隆，同时正常c-myc等位基因的表达丧失。这些克隆在表型上是正常的，但是，在根据Luria和Delbrück（1943年）对来自同一克隆独立传代培养的细胞进行的波动试验中，转化灶作为具有广泛波动范围的随机事件出现。这些结果表明癌基因的表达不足以诱导转化生长特性的出现，并且需要二次遗传变化，最有可能是细胞原癌基因中的突变。在单个克隆内，独立的转化体表现出不同的致瘤潜力，从高效到无明显的肿瘤诱导，与它们的体外转化程度没有任何明显的相关性。从独立肿瘤建立的肿瘤和细胞系，在不改变其结构的情况下保持外源myc基因，不再表达癌基因并恢复正常等位基因的表达。
