Xie D-X, Yao J, Zhang P, Li X-L, Feng Y-D, Wu J-H, Tao D-D, Hu J-B, Gong J-P
Tongji Cancer Research Institute, Tongji Hospital, Tongji Medical College in Huazhong University of Science and Technology, Wuhan, China.
Cell Prolif. 2008 Apr;41(2):265-78. doi: 10.1111/j.1365-2184.2008.00518.x.
Based on studies of unicellular organisms or cultured mammalian cells, the generally accepted model of cell-cycle regulation has been developed in which sequential (scheduled) expression of cyclins D, E, A and B and activation of Cdk2 and Cdk1 takes place. It is assumed that the same model is applicable both in vivo and in vitro.
In the present study, we compared proliferating marrow cells freshly isolated from healthy individuals with proliferating lymphocytes in cultures.
We demonstrate that during progression of freshly collected human bone marrow cells through G(1), S and G(2)/M, only Cdk1 combined with cyclins A and B(1) was distinctly present and active, and its activity gradually increased. In contrast, in vitro growing mitogen-stimulated lymphocytes had perfectly scheduled sequential expression of all four cyclins and Cdk1 and Cdk2 activities.
Our findings demonstrate that the pattern of cyclin expression and Cdk activity in bone marrow in vivo is distinctly different from the one observed for normal cells in vitro. Because proliferating bone marrow cells are predominantly expanding populations of committed progenitors, it is likely that during the expansion phase their cell-cycle progression is pre-programmed, being driven solely by Cdk1 combined either with cyclin A or with cyclin B(1). Expansion of progenitor cells thus may not require the early steps of cell-cycle regulation, associated with triggering progression by availability of growth factors and mitogens.
基于对单细胞生物或培养的哺乳动物细胞的研究，已建立了普遍接受的细胞周期调控模型，其中细胞周期蛋白D、E、A和B依次（按计划）表达，细胞周期蛋白依赖性激酶2（Cdk2）和细胞周期蛋白依赖性激酶1（Cdk1）被激活。假定同一模型在体内和体外均适用。
在本研究中，我们将从健康个体新鲜分离的增殖骨髓细胞与培养中的增殖淋巴细胞进行了比较。
我们证明，在新鲜采集的人骨髓细胞通过G1、S和G2/M期的过程中，只有与细胞周期蛋白A和B1结合的Cdk1明显存在且具有活性，并且其活性逐渐增加。相比之下，体外生长的有丝分裂原刺激的淋巴细胞具有所有四种细胞周期蛋白以及Cdk1和Cdk2活性的完美按计划的顺序表达。
我们的研究结果表明，体内骨髓中细胞周期蛋白表达模式和Cdk活性与体外正常细胞中观察到的明显不同。由于增殖的骨髓细胞主要是定向祖细胞的扩增群体，因此在扩增阶段它们的细胞周期进程可能是预先编程的，仅由与细胞周期蛋白A或细胞周期蛋白B1结合的Cdk1驱动。因此，祖细胞的扩增可能不需要细胞周期调控的早期步骤，即通过生长因子和有丝分裂原的可用性触发进程。
