Naik P, Karrim J, Hanahan D
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0534, USA.
Genes Dev. 1996 Sep 1;10(17):2105-16. doi: 10.1101/gad.10.17.2105.
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-xL was up-regulated in tumors. When overexpressed throughout the pathway, bcl-xL 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.
在胰岛β细胞多阶段肿瘤发生的小鼠模型中，凋亡与T抗原癌基因诱导的细胞增殖同时被激活，在血管生成阶段进一步增加，而在实体瘤中显著减少。与p53基因敲除小鼠杂交证实了这种阶段特异性变化是一个不依赖p53的凋亡过程。几种凋亡调节因子被表达，其中bcl-xL在肿瘤中上调。当在整个通路中过表达时，bcl-xL保护大多数表达癌基因的细胞免于凋亡，增强从血管生成祖细胞到肿瘤的进展，而不影响早期转变。此外，描述了两类实体瘤，根据大小和凋亡发生率区分，提示凋亡调节在肿瘤扩张性生长中的作用。因此，凋亡的下调选择性地促进肿瘤发生途径中的后期步骤。
