Kastan M B, Canman C E, Leonard C J
Johns Hopkins Oncology Center, Baltimore, Maryland, USA.
Cancer Metastasis Rev. 1995 Mar;14(1):3-15. doi: 10.1007/BF00690207.
Cellular proliferation depends on the rates of both cell division and cell death. Tumors frequently have decreased cell death as a primary mode of increased cell proliferation. Genetic changes resulting in loss of programmed cell death (apoptosis) are likely to be critical components of tumorigenesis. Many of the gene products which appear to control apoptotic tendencies are regulators of cell cycle progression; thus, cell cycle control and cell death appear to be tightly linked processes. P53 protein is an example of a gene product which affects both cell cycle progression and apoptosis. The ability of p53 overexpression to induce apoptosis may be a major reason why tumor cells frequently disable p53 during the transformation process. Unfortunately, the same genetic changes which cause loss of apoptosis during tumor development, may also result in tumor cell resistance to anti-neoplastic therapies which kill tumor cells by apoptosis. Elucidation of the genetic and biochemical controls of these cellular responses may provide insights into ways to induce cell death and thus hopefully suggest new targets for improving therapeutic index in the treatment of malignancies.
细胞增殖取决于细胞分裂和细胞死亡的速率。肿瘤常常通过降低细胞死亡作为增加细胞增殖的主要方式。导致程序性细胞死亡（凋亡）缺失的基因变化可能是肿瘤发生的关键组成部分。许多似乎控制凋亡倾向的基因产物是细胞周期进程的调节因子；因此，细胞周期控制和细胞死亡似乎是紧密相连的过程。P53蛋白就是一个影响细胞周期进程和凋亡的基因产物的例子。p53过表达诱导凋亡的能力可能是肿瘤细胞在转化过程中常常使p53失活的主要原因。不幸的是，在肿瘤发展过程中导致凋亡缺失的相同基因变化，也可能导致肿瘤细胞对抗肿瘤治疗产生耐药性，这些治疗通过凋亡来杀死肿瘤细胞。阐明这些细胞反应的遗传和生化控制可能为诱导细胞死亡的方法提供见解，从而有望为改善恶性肿瘤治疗的治疗指数提出新的靶点。
