Rb+/+和Rb-/-小鼠胚胎成纤维细胞以及骨肉瘤细胞系G1期调控的数学模型。
A mathematical model of the regulation of the G1 phase of Rb+/+ and Rb-/- mouse embryonic fibroblasts and an osteosarcoma cell line.
作者信息
Obeyesekere M N, Knudsen E S, Wang J Y, Zimmerman S O
机构信息
Department of Biomathematics, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
出版信息
Cell Prolif. 1997 Mar-Apr;30(3-4):171-94. doi: 10.1046/j.1365-2184.1997.00078.x.
A mathematical model integrating the roles of cyclin D, cdk4, cyclin E, cdk2, E2F and RB in control of the G1 phase of the cell cycle is described. Experimental results described with murine embryo fibroblasts (MEFs), either Rb+/+ or Rb-/-, and with the RB-deficient osteosarcoma cell line, Saos-2, served as the basis for the formulation of this mathematical model. A model employing the known interactions of these six proteins does not reproduce the experimental observations described in the MEFs. The appropriate modelling of G1 requires the inclusion of a sensing mechanism which adjusts the activity of cyclin E/cdk2 in response to both RB concentration and growth factors. Incorporation of this sensing mechanism into the model allows it to reproduce most of the experimental results observed in Saos-2 cells, Rb-/- MEFS, and Rb+/+ MEFs. The model also makes specific predictions which have not been tested experimentally.
描述了一个整合细胞周期蛋白D、细胞周期蛋白依赖性激酶4（cdk4）、细胞周期蛋白E、细胞周期蛋白依赖性激酶2（cdk2）、E2F和视网膜母细胞瘤蛋白（RB）在控制细胞周期G1期作用的数学模型。用野生型或敲除Rb基因的小鼠胚胎成纤维细胞（MEF）以及RB缺陷型骨肉瘤细胞系Saos-2所描述的实验结果，作为构建此数学模型的基础。一个采用这六种蛋白质已知相互作用的模型无法重现MEF中描述的实验观察结果。对G1期进行适当建模需要纳入一种传感机制，该机制可根据RB浓度和生长因子来调节细胞周期蛋白E/cdk2的活性。将这种传感机制纳入模型后，它能够重现Saos-2细胞、敲除Rb基因的MEF和野生型MEF中观察到的大多数实验结果。该模型还做出了尚未经过实验验证的具体预测。
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