Campisi J, Gray H E, Pardee A B, Dean M, Sonenshein G E
Cell. 1984 Feb;36(2):241-7. doi: 10.1016/0092-8674(84)90217-4.
Cellular oncogenes are DNA sequences implicated in the genesis of cancer, but their functions in the transformation process are not understood. Our experiments provide data linking expression of two well-studied proto-oncogenes, c-myc and c-rasKi, to current knowledge of proliferation control and its perturbation by differentiation and chemical transformation. Growth stimulation of quiescent cells by serum elevates expression of the myc proto-oncogene in Balb/c 3T3 (A31) cells. In two chemically transformed A31 derivatives (BPA31 and DA31), c-myc expression is constitutive. The levels of c-myc mRNA in quiescent and growing transformed cells are nearly the same, and are only slightly elevated compared to the level found in growing A31 cells. By contrast, c-rasKi expression is cell-cycle-dependent in BPA31 cells. The relative abundance of c-rasKi mRNA begins to increase in mid- to late G0/G1. During terminal differentiation of teratocarcinoma stem cells (F9) into nonproliferating endoderm, relative mRNA abundance is diminished more markedly for c-myc than for c-rasKi. These results demonstrate that expression of the myc and rasKi proto-oncogenes is dependent upon the cellular growth state, and that growth control exhibits growth-factor-dependent, cell-cycle-timed oncogene expression. In the case of the BPA31 cells, c-myc is not rearranged, amplified, or overexpressed. However, the oncogene has lost its cycle-dependent regulation in the chemically transformed cells.
细胞癌基因是与癌症发生有关的DNA序列，但其在转化过程中的功能尚不清楚。我们的实验提供了数据，将两个经过充分研究的原癌基因c-myc和c-rasKi的表达与目前关于增殖控制及其受分化和化学转化干扰的知识联系起来。血清对静止细胞的生长刺激可提高Balb/c 3T3（A31）细胞中原癌基因myc的表达。在两种化学转化的A31衍生物（BPA31和DA31）中，c-myc表达是组成型的。静止和生长的转化细胞中c-myc mRNA的水平几乎相同，与生长的A31细胞中发现的水平相比仅略有升高。相比之下，c-rasKi在BPA31细胞中的表达是细胞周期依赖性的。c-rasKi mRNA的相对丰度在G0/G1中期到后期开始增加。在畸胎癌干细胞（F9）向非增殖性内胚层的终末分化过程中，c-myc的相对mRNA丰度比c-rasKi下降得更明显。这些结果表明，myc和rasKi原癌基因的表达取决于细胞生长状态，并且生长控制表现出生长因子依赖性、细胞周期定时的癌基因表达。就BPA31细胞而言，c-myc没有重排、扩增或过度表达。然而，在化学转化的细胞中，癌基因失去了其周期依赖性调节。
