周期素A过表达诱导S期细胞凋亡的研究

Overexpression of Cyclin A Leads to S-phase Arrested Apoptosis

目的 探讨细胞周期 S期滞留细胞凋亡的分子基础。方法 用 Westernblot法测定 L- 2和 Br1-3pr- 1两细胞株细胞周期 S期进程相关分子 Rb、周期素 A、E、CDK2、CDC2及与细胞凋亡直接相关分子 Bcl- 2和Bax的表达 ,并用组蛋白磷酸化法测定周期素 A、E、CDK2和 CDC2相关激酶的活性。结果 经 PAL A处理后 ,发生 S期细胞凋亡的 L- 2细胞与不发生 S期细胞凋亡的 Br1- 3pr- 1细胞比较 ,其周期素 A的表达明显增加 ,Bcl- 2的表达下降。但经 PAL A处理后 ,其他分子的表达和激酶活性在上述两种细胞之间无明显差异。结论 周期素 A可能是 S期检查点基因的重要候选者 ,并可能通过调节 Bcl- 2的表达来控制 S期滞留细胞凋亡的发生。

Objective This study was aimed to gain an insight into the molecular basis of S phase arrest associated apoptosis. Methods The molecular expressions of Rb, cyclin A, cyclin E, CDK2 and CDC2 involved in S phase progression were investigated by westernblot in L 2 and Br1 3pr 1 cells. Furthermore, their associated kinase activities were assayed by histone 1 phosphorylation. Results The results showed that ofter PALA treatment, the expression of cyclin A increased and the expression of Bcl 2 decreased in apoptosising L 2 cell as compared with those in unapoptosising Br1 3pr 1 cell, but there were no significant differences in other molecular expressions and associated kinase activities between the above mentioned L 2 cell and Br1 3pr 1 cell arrested at S phase after PALA treatment. Conclusion Cyclin A is a most potential candidate for S phase checkpoint element, and it may be able to induce the S phase arrest associated apoptosis through the Bcl 2 pathway.