Prevalent deficiency in tumor cells of cycloheximide-induced cycle arrest.
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.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D014176:Protein Biosynthesis
D003513:Cycloheximide