Wei W, Nurse P, Broek D
Department of Biochemistry and Molecular Biology, Kenneth Norris Jr. Cancer Hospital and Research Institute, University of Southern California School of Medicine, Los Angeles 90033.
Cancer Res. 1993 Apr 15;53(8):1867-70.
We have examined the ability of the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae to enter a quiescent state through G1, S, G2, or M phase of the cell cycle. We monitored entry to a quiescent state by measuring two well known properties of quiescent cells, i.e., long-term viability and a dramatic increase in resistance to thermal heat shock relative to cycling cells. For this purpose, we made use of yeast cell division cycle (cdc) mutants with which we could arrest most of the cells in culture at specific points in the cell cycle. We find that these eukaryotes can enter a reversible quiescent state at any of the points in the cell cycle we examined if the cells are exposed to starvation conditions (starvation normally signals cells to leave the cell cycle). These findings indicate that mechanisms involved in entry to and exit from a quiescent state can operate not only in G1 phase (leading to G0 arrested cells) but can also operate in S, G2, and M phases of the cell cycle. These findings may be important for clinical oncology in cases where tumor cells escape the cytotoxic effects of chemotherapeutic agents. It may be that escape from the effect of these drugs is due to tumor cells entering quiescent states at points in the cell cycle other than G1 phase. Perhaps different chemotherapeutic strategies may be required to kill tumor cells reentering the cell cycle from other than G1.
我们研究了粟酒裂殖酵母和酿酒酵母通过细胞周期的G1、S、G2或M期进入静止状态的能力。我们通过测量静止细胞的两个众所周知的特性来监测进入静止状态的情况,即长期活力以及相对于处于细胞周期循环中的细胞而言,对热休克的抗性显著增加。为此,我们利用了酵母细胞分裂周期(cdc)突变体,通过这些突变体我们可以使培养中的大多数细胞在细胞周期的特定点停滞。我们发现,如果细胞暴露于饥饿条件下(饥饿通常会促使细胞离开细胞周期),这些真核生物在我们检测的细胞周期的任何点都能进入可逆的静止状态。这些发现表明,参与进入和退出静止状态的机制不仅可以在G1期(导致细胞停滞在G0期)发挥作用,也可以在细胞周期的S、G2和M期发挥作用。这些发现对于临床肿瘤学可能很重要,例如在肿瘤细胞逃避化疗药物细胞毒性作用的情况下。可能这些药物效果不佳是由于肿瘤细胞在细胞周期中除G1期之外的其他点进入了静止状态。也许需要不同的化疗策略来杀死从G1期以外的其他阶段重新进入细胞周期的肿瘤细胞。