Wyllie A H
Department of Pathology, University Medical School, Edinburgh, UK.
Br J Cancer. 1993 Feb;67(2):205-8. doi: 10.1038/bjc.1993.40.
Apoptosis is a mode of cell death with characteristic structural features. These appear to result from a set of discrete cellular events that are regulated by gene expression. Oncogenesis and oncosuppressor genes are involved in this regulation. The role of c-myc is of particular interest, as it can act as a bivalent regulator, determining either cell proliferation or apoptosis, depending on whether free movement around the cell cycle is supported (by growth factors) or is limited by growth factor deprivation or treatment with other cycle-blocking agents. In vivo, c-myc expression may be associated with a 'high-turnover' state in which cell proliferation and apoptosis co-exist. Certain other oncogenes (e.g. ras, bcl-2) rescue cells from susceptibility to apoptosis and so convert this high-turnover state into rapid population expansion. One role of the oncosuppressor gene p53 may be to initiate apoptosis by causing G 1/S arrest in cells expressing c-myc. Some aspects of resistance and sensitivity to chemotherapeutic agents can be explained on the basis of movement between the population-expansion and the high-turnover states, perhaps through modulation of the expression of these and other genes.
细胞凋亡是一种具有特征性结构特征的细胞死亡方式。这些特征似乎源于一系列由基因表达调控的离散细胞事件。肿瘤发生基因和抑癌基因参与了这一调控过程。c-myc的作用尤其令人关注，因为它可以作为一种双价调节因子，根据细胞周期的自由运转是否得到支持（由生长因子支持）或受到生长因子剥夺或其他周期阻断剂处理的限制，决定细胞增殖或凋亡。在体内，c-myc表达可能与一种“高周转率”状态相关，在这种状态下细胞增殖和凋亡并存。某些其他癌基因（如ras、bcl-2）可使细胞免于凋亡易感性，从而将这种高周转率状态转变为快速的群体扩张。抑癌基因p53的一个作用可能是通过在表达c-myc的细胞中引起G1/S期阻滞来启动凋亡。对化疗药物的耐药性和敏感性的某些方面可以基于群体扩张状态和高周转率状态之间的转变来解释，这可能是通过调节这些基因和其他基因的表达实现的。
