CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species
CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species
复制标题
DOI：
10.1016/j.bbrc.2012.07.059
复制
发表时间：
2012-08-17
影响因子：
3.1
通讯作者：
Kwon, Ki-Sun
中科院分区：
文献类型：
--
作者：
Hwang, Chae Young;Lee, Seung-Min;Kwon, Ki-Sun
活性氧以环境依赖的方式调节细胞命运。亚致死剂量的H2 O2降低了正常细胞（包括原代人皮肤成纤维细胞和IMR-90细胞）中增殖细胞核抗原（PCNA）的水平，而不影响细胞周期蛋白依赖性激酶2（CDK 2）的活性，导致细胞周期停滞和随后的衰老。相反，将癌细胞（如HeLa和MCF 7细胞）暴露于H2 O2增加了CDK 2活性，而没有伴随PCNA水平的变化，导致细胞增殖。CDK 2抑制剂CVT-313可阻止H2 O2诱导的癌细胞增殖。这些结果支持了这样的观点，即细胞周期蛋白/CDK 2/p21（Cip 1）/PCNA复合物作为细胞命运决定的调节器起着重要作用。(C)2012 Elsevier Inc. All rights reserved.
Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H2O2 decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H2O2 increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H2O2-induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21(Cip1)/PCNA complex plays an important role as a regulator of cell fate decisions. (C) 2012 Elsevier Inc. All rights reserved.