Circadian variation in the expression of cell-cycle proteins in human oral epithelium
Circadian variation in the expression of cell-cycle proteins in human oral epithelium
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DOI：
10.1016/s0002-9440(10)65306-0
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发表时间：
1999-02-01
影响因子：
6
通讯作者：
Sothern, RB
中科院分区：
文献类型：
--
作者：
Bjarnason, GA;Jordan, RCK;Sothern, RB
在组织水平上，有实验和临床数据表明细胞周期的细胞动力学协调，在一天中的特定时间，更大比例的循环细胞进入s期和有丝分裂。某些细胞周期蛋白与细胞周期中定义的事件的关联已经很好地建立起来，并可用于研究24小时内细胞周期阶段的时间。在这项研究中，对6名正常的人类志愿者进行口腔粘膜活检，每隔4小时进行一次，24小时内进行6次。利用免疫组织化学，在每次活检中测定表达p53、cyclin- e、cyclin- a、cyclin B1和Ki-67蛋白的阳性细胞数量，并以每毫米基底膜的阳性细胞数量表示。我们发现所有这些蛋白的细胞核表达有统计学上显著的昼夜变化，p53的高表达点在10:56小时，cycline在14:59小时，cyclina在16:09小时，cyclinb1在21:13小时，Ki-67在02:50小时。周期蛋白- e （G1/S期）、-A （g2期）和-B1 （m期）的核表达随着时间的正常生理进展的昼夜节律变化表明，口腔上皮细胞增殖的昼夜节律变化具有统计学意义。发现与G1晚期相对应的p53蛋白核表达的昼夜变化是新颖的。这一信息对化疗和放疗的时机具有临床意义。
At the tissue level, there is experimental and clinical data to suggest a cytokinetic coordination of the cell cycle with a greater proportion of cycling cells entering S-phase and mitosis at specific times of the day. The association of certain cell-cycle proteins with defined events in the cell cycle is well established and may be used to study the timing of cell-cycle phases over 24 hours. In this study oral mucosal biopsies were obtained from six normal human volunteers at 4-hour intervals, six times over 24 hours. Using immunohistochemistry, the number of positive cells expressing the proteins p53, cyclin-E, cyclin-A, cyclin B1, and Ki-67 was determined for each biopsy and expressed as the number of positive cells per mm of basement membrane. We found a statistically significant circadian variation in the nuclear expression of all of these proteins with the high point of expression for p53 at 10:56 hours, cyclin-E at 14:59 hours, cyclin-A at 16:09 hours, cyclin-B1 at 21:13 hours, and Ki-67 at 02:50 hours. The circadian variation in the nuclear expression of cyclins-E (G1/S phase), -A (G2-phase), and -B1 (M-phase) with a normal physiological progression over time suggests a statistically significant circadian variation in oral epithelial cell proliferation. The finding of a circadian variation in the nuclear expression of p53 protein corresponding to late G1 is novel. This information has clinical implications regarding the timing of chemotherapy and radiotherapy.