Kao G D, McKenna W G, Maity A, Blank K, Muschel R J
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Cancer Res. 1997 Feb 15;57(4):753-8.
Irradiation of tumor cells results in a G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is marked in HeLa and other cells by delayed expression of cyclin B1. To test whether this depression of cyclin B1 contributes to the G2 delay, we induced cyclin B1 expression in irradiated HeLa cells using a dexamethasone-inducible promoter. Induction of cyclin B1 after radiation abrogated the G2 delay by approximately doubling the rate at which the cells reentered mitosis, whereas dexamethasone itself had no effect. However, overexpression of cyclin B1 did not eliminate the G2 delay in irradiated cells. In unirradiated cells, overexpression of cyclin B1 had no effect on cell cycle progression. Confirmation that reduction of cyclin B1 levels would prolong G2 was provided using antisense oligonucleotides to cyclin B1. These results demonstrate that cyclin B1 levels control the length of the G2 delay following irradiation in HeLa cells but do not exclude additional mechanisms controlling the mitotic delay after irradiation.
肿瘤细胞受到照射会导致G2期延迟，据推测这是为了使DNA得以修复并让细胞存活。在HeLa细胞和其他细胞中，照射后的G2期延迟表现为细胞周期蛋白B1的表达延迟。为了测试细胞周期蛋白B1的这种下调是否导致了G2期延迟，我们使用地塞米松诱导型启动子在受照射的HeLa细胞中诱导细胞周期蛋白B1的表达。辐射后诱导细胞周期蛋白B1的表达消除了G2期延迟，细胞重新进入有丝分裂的速率大约增加了一倍，而地塞米松本身则没有效果。然而，细胞周期蛋白B1的过表达并未消除受照射细胞中的G2期延迟。在未受照射的细胞中，细胞周期蛋白B1的过表达对细胞周期进程没有影响。使用针对细胞周期蛋白B1的反义寡核苷酸证实了细胞周期蛋白B1水平的降低会延长G2期。这些结果表明，细胞周期蛋白B1的水平控制着HeLa细胞照射后G2期延迟的时长，但并不排除存在其他控制照射后有丝分裂延迟的机制。
