Paradoxical role of apoptosis in tumor progression
Paradoxical role of apoptosis in tumor progression
复制标题
DOI：
10.1002/jcb.10382
复制
发表时间：
2003-01-01
影响因子：
4
通讯作者：
Gudkov, AV
中科院分区：
文献类型：
--
作者：
Gurova, KV;Gudkov, AV
肿瘤经常获得对细胞凋亡的抵抗，这可能会导致恶性表型，降低对治疗的敏感性。事实上，p53肿瘤抑制基因失活导致细胞凋亡被抑制是一个阴性预后指标。令人惊讶的是，一种强抗凋亡蛋白Bcl-2的表达，另一种避免细胞凋亡的机制，被发现与良好的预后有关。基于Bcl-2对细胞增殖的负面作用，已有文献解释了Bcl-2的这种矛盾的抗进展功能。在这里，通过分析积累的实验和临床数据，我们提供证据支持另一种假设，即细胞凋亡是肿瘤进展的加速器。Bcl-2抗进展功能的机制是基于肿瘤的产生，通过消除通过p53丧失获得凋亡抗性的细胞的选择优势来维持对基因组稳定性的控制。因此，抑制细胞凋亡并不会导致基因组稳定性的丧失，而是产生不再支持肿瘤进一步发展的肿瘤环境，细胞凋亡抑制剂可以被认为是抑制肿瘤进展的因素。(C) 2002 Wiley-Liss, Inc。
Tumors frequently acquire resistance to apoptosis that is expected to contribute to malignant phenotype and reduce sensitivity to treatment. In fact, inactivation of p53 tumor suppressor gene resulting in suppression of apoptosis serves as a negative prognostic marker. Surprisingly, expression of a strong anti-apoptotic protein Bcl-2, another mechanism to avoid apoptosis, was found to be associated with a favorable prognosis. This paradoxical anti-progressor function of Bcl-2 has been explained in literature based on the negative effect of Bcl-2 on cell proliferation. Here, by analyzing accumulated experimental and clinical data, we provide evidence supporting another hypothesis that defines apoptosis as an accelerator of tumor progression. The mechanism of anti-progressor function of Bcl-2 is based on creation of tumors that maintain control of genomic stability by eliminating selective advantages for the cells that acquire resistance to apoptosis through loss of p53. Thus, inhibition of apoptosis does not lead to loss of genomic stability and creates tumor environment that no longer supports further tumor progression and inhibitors of apoptosis can be considered as factors suppressing tumor progression. (C) 2002 Wiley-Liss, Inc.