Prevalent deficiency in tumor cells of cycloheximide-induced cycle arrest.
Prevalent deficiency in tumor cells of cycloheximide-induced cycle arrest.
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肿瘤细胞普遍缺乏放线菌酮诱导的周期停滞。
DOI：
10.1073/pnas.77.7.4123
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发表时间：
1980
影响因子：
11.1
通讯作者：
Pardee,AB
中科院分区：
文献类型：
--
作者：
Medrano,EE;Pardee,AB
哺乳动物细胞的生长受一个过程的调节，该过程在周期的G1晚期部分的限制点完成。该过程对血清浓度高度敏感，并对放线菌酮（CHM）或其他药物对蛋白质合成的中度抑制高度敏感。我们已经提出，细胞必须积累一个临界量的不稳定蛋白质，然后才能开始与DNA合成有关的事件。这种蛋白质的积累需要适合生长的条件，包括足够量的血清衍生因子。将主要作用归于这种调节机制的一个重要标准是生长控制被修饰的细胞--例如，在这个过程中应该是有缺陷的。这类细胞是通过致瘤转化产生的。我们在这里显示，小鼠3 T3细胞，人成纤维细胞，和中国仓鼠CHEF/18细胞具有严格的G1期生长控制CHM。相反，通过用各种试剂（DNA肿瘤病毒、RNA肿瘤病毒、化学致癌物）转化或自发地从这些细胞获得的致瘤细胞系在CHM的影响下均显示松弛的生长控制。在这些品系中，生长控制放松到不同程度;一些品系通过低血清浓度和CHM的组合保持在G1期，但其他品系则没有。血清浓度与中药呈协同作用。低血清浓度不仅通过影响蛋白质合成速率来限制生长。不稳定蛋白质机制可能是血清因子控制生长的基础。转化的致瘤细胞通常可能放松了这种机制。
Mammalian cell growth is regulated by a process that is completed at a restriction point in the late G1 part of the cycle. This process is highly sensitive to serum concentration and to moderate inhibition of protein synthesis by cycloheximide (CHM) or other agents. We have proposed that a cell must accumulate a labile protein in a critical amount before events related to its DNA synthesis can start. The accumulation of this protein requires conditions suitable for growth, including sufficient amounts of serum-derived factors. An important criterion for attributing a major role to such a regulatory mechanism is that cells whose growth control is modified--e.g., by mutation--should be defective in this process. Cells of this kind are produced by tumorigenic transformation. We show here that mouse 3T3 cells, human fibroblasts, and Chinese hamster CHEF/18 cells have stringent G1 growth control by CHM. In contrast, tumorigenic lines obtained from these cells by transformation with varius agents (DNA tumor virus, RNA tumor virus, chemical carcinogens) or spontaneously all showed relaxed growth control under the influence of CHM. In these lines, growth control was relaxed to different degrees; some lines were held in G1 by a combination of low serum concentration and CHM, but others were not. Serum concentration showed a synergistic effect with CHM. Low serum concentrations did not limit growth only by affecting the rate of protein synthesis. The labile-protein mechanism is likely to be basic to growth control by serum factors. Transformed tumorigenic cells in general may have relaxed this mechanism.