Graff Pål, Amellem Oystein, Seim Jo, Stokke Trond, Pettersen Erik O
Department of Physics, The Biophysics Group, University of Oslo, P.O. Box 1048 Blindern, 0316 Oslo, Norway.
Anticancer Res. 2005 May-Jun;25(3B):2259-67.
We have studied hypoxia-induced cell cycle arrest in human cells where the retinoblastoma tumour suppressor protein (pRb) is either functional (T-47D cells) or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells). Cells of both types are arrested in a restriction point in late G1, here denoted as the oxygen-dependent restriction point in late G1. This arrest seems to occur under extreme hypoxia in all types of mammalian cells so far tested. During an 18-h exposure to extreme hypoxia, the p27 protein level increased in G1-phase in both cells lines investigated and was followed by a binding between p27 and CDK2. This was observed both in the pRb-positive T-47D cells and in the pRb-negative NHIK 3025 cells. We, therefore, believe that p27 and not pRb is the mediator of this oxygen-dependent checkpoint in late G1. Our results also suggest that p27 regulates the restart of cell cycle progression of these arrested cells after reoxygenation.
我们研究了缺氧诱导的人类细胞周期停滞情况，其中视网膜母细胞瘤肿瘤抑制蛋白（pRb）要么功能正常（T-47D细胞），要么因HPV18 E7癌蛋白的表达而失活（NHIK 3025细胞）。这两种类型的细胞都停滞在G1晚期的一个限制点，在此称为G1晚期的氧依赖性限制点。迄今为止测试的所有类型的哺乳动物细胞在极端缺氧情况下似乎都会发生这种停滞。在暴露于极端缺氧环境18小时期间，所研究的两种细胞系中G1期的p27蛋白水平均升高，随后p27与CDK2结合。在pRb阳性的T-47D细胞和pRb阴性的NHIK 3025细胞中均观察到这种情况。因此，我们认为p27而非pRb是G1晚期这种氧依赖性检查点的介导因子。我们的结果还表明，p27调节这些停滞细胞复氧后细胞周期进程的重新启动。
