Qin Ji-Chao, Chen Xiao-Xi, Tao De-Ding, Feng Yong-Dong, Hu Jun-Bo, Gong Jian-Ping
Center of Gastroenterological Surgery/Cancer Research Institute, Tongji Hospital, Tongji Medical College, University of Huazhong Science and Technology, Wuhan, Hubei 430 030, P.R. China.
Ai Zheng. 2004 Nov;23(11):1244-8.
BACKGROUND & OBJECTIVE: Many studies showed that high expression of Cyclin E promotes cell proliferation, but contrary data was also reported that cell proliferation didn't decrease with low expression of Cyclin E. In addition, we observed that many tumor cells have strong capability of proliferation with low expression of Cyclins, including Cyclin E. This study was to analyze effect of reduced Cyclin E threshold on proliferation of acute lymphocyte leukemia cell line MOLT-4 to explain the above phenomena.
We have established the model of decreased Cyclin E threshold in MOLT-4 cells by treating cells with low concentration (5 mmol/L) of caffeine for 2, and 4 h. The positive rates of proliferation cell nuclear antigen (PCNA), Ki67, and DNA strand break induction by photolysis (SBIP) were analyzed by flow cytometry.
MOLT-4 cells presented sharply decrease of Cyclin E threshold, and increase of positive rates of PCNA, Ki67, and SBIP after treated with caffeine, especially at 2-h point.
Decrease of Cyclin E threshold was accompanied by increase of cell proliferation. MOLT-4 cells may remain high proliferation capability with low level of Cyclin expression.
许多研究表明细胞周期蛋白E(Cyclin E)的高表达促进细胞增殖,但也有相反的数据报道,即Cyclin E低表达时细胞增殖并未降低。此外,我们观察到许多肿瘤细胞在包括Cyclin E在内的细胞周期蛋白低表达时仍具有很强的增殖能力。本研究旨在分析降低Cyclin E阈值对急性淋巴细胞白血病细胞系MOLT-4增殖的影响,以解释上述现象。
通过用低浓度(5 mmol/L)咖啡因处理MOLT-4细胞2小时和4小时,建立了降低Cyclin E阈值的模型。采用流式细胞术分析增殖细胞核抗原(PCNA)、Ki67的阳性率以及光解诱导的DNA链断裂(SBIP)情况。
咖啡因处理后,MOLT-4细胞的Cyclin E阈值急剧降低,PCNA、Ki67的阳性率以及SBIP增加,尤其是在处理2小时时。
Cyclin E阈值降低伴随着细胞增殖增加。MOLT-4细胞在细胞周期蛋白低水平时可能仍保持高增殖能力。