ERK和P38信号转导途径对慢性髓系白血病细胞周期的调控作用

本研究探讨ERK和P38信号转导途径对慢性髓系白血病（CML）细胞周期的调控作用。以RT-PCR、Western blot和FCM方法分别检测CML患者白血病细胞和K562细胞中ERK、p38、cyclin D2、cyclin E、p27的mRNA表达及蛋白表达（其中ERK和P38为磷酸化ERK和磷酸化P38）及细胞周期分布,并分析其相关关系。结果表明：CML患者白血病细胞和K562细胞中ERK、P38、cyclin D2、cyclin E的mRNA表达和蛋白表达增高,P27的表达降低,且cyclin D2蛋白表达与cyclin E、ERK和P38蛋白表达呈正相关（P〈0.01）,与P27蛋白表达呈负相关（P〈0.01）。G0/G1期细胞减少,S期细胞增多,与对照组相比有显著性差异。结论：CML中P38、ERK mRNA表达和活性增加,激活下游的cyclin D2、cyclin E和P27等细胞周期调控因子,致使G0/G1期缩短,细胞快速通过G1/S转换点进入S期,加速细胞周期进程和细胞增殖,导致CML的发生。

Regulative Effects of ERK and P38 Signal Transduction Pathway on Cell Cycle in Chronic Myeloid Leukemia

This study was aimed to investigate the regulative effect of ERK and p38 signal transduction pathway on cell cycle of CML. The mRNA and protein expression of ERK, p38,cyclin D2, cyclin E and p27 (ERK and p38 were Phosph-ERK and Phosph-P38) in CML cells and K562 cell lines were detected by RT-PCR and Western blot, respectively; cell cycle was determined by FCM, and their relationship was analyzed. The results showed that the mRNA and protein expressions of ERK, p38,cyclin D2 and cyclin E in CML cells and K562 cells increased (P<0.01) and the expression of p27 decreased (P<0.01). There was positive correlation between the protein expressions of cyclin D2 and the protein expreesion of ERK, p38 and cyclin E, but there was negative correlation between the protein expressions of cyclin D2 and the protein expression of p27. The percentage of cells in G0/G1 phase was decreased and the percentage of cells in S phase was increased, there was significant difference as compared with control (P<0.05). It is concluded that increase of the mRNA expression and protein activity of ERK and p38 activate the cell cycle-regulating proteins such as cyclin D2 ,cyclin E,p27 which results in shortening of G0/G1 phase, switching cell to S phase through G1/S check point quickly and accelerating cell cycle progression and cell proliferation, and eventually leads to occurence of CML.