The rise and fall of apoptosis during multistage tumorigenesis: Down-modulation contributes to tumor progression from angiogenic progenitors
The rise and fall of apoptosis during multistage tumorigenesis: Down-modulation contributes to tumor progression from angiogenic progenitors
复制标题
DOI：
10.1101/gad.10.17.2105
复制
发表时间：
1996-09-01
影响因子：
10.5
通讯作者：
Hanahan, D
中科院分区：
文献类型：
--
作者：
Naik, P;Karrim, J;Hanahan, D
在胰岛β细胞多阶段肿瘤发生的小鼠模型中，细胞凋亡伴随T抗原癌基因诱导的细胞增殖而被激活，在血管生成阶段进一步增加，在实体瘤中显著减少。与p53基因缺失小鼠的杂交证实了这种阶段特异性变异是一种不依赖于p53的凋亡过程。几种凋亡调节因子表达，其中bcl-x（L）在肿瘤中上调。当在整个通路中过度表达时，bcl-x（L）保护大多数癌基因表达细胞免于凋亡，促进从血管生成祖细胞到肿瘤的进展，而不影响早期转化。此外，描述了两类实体瘤，其通过大小和凋亡发生率来区分，这涉及在膨胀性肿瘤生长中的凋亡调节。因此，细胞凋亡的下调选择性地有助于肿瘤发生途径中的晚期步骤。
In a mouse model of multistage tumorigenesis of islet beta-cells, apoptosis was activated concomitant with T-antigen oncogene-induced cell proliferation, further increased in the angiogenic stage, and markedly reduced in solid tumors. Crosses to p53-null mice confirmed this stage-specific variation as a p53-independent apoptotic process. Several apoptosis regulators were expressed, of which bcl-x(L) was up-regulated in tumors. When overexpressed throughout the pathway, bcl-x(L) protected most oncogene-expressing cells from apoptosis, enhancing progression from angiogenic progenitor to tumor without affecting earlier transitions. Further, two classes of solid tumor are described, distinguished by size and apoptotic incidence, implicating apoptosis regulation in expansive tumor growth. Thus, down-modulation of apoptosis selectively contributes to late steps in a tumorigenesis pathway.