Uncoupling of cell growth and proliferation results in enhancement of productivity in p21C1P1-arrested CHO cells
Uncoupling of cell growth and proliferation results in enhancement of productivity in p21C1P1-arrested CHO cells
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DOI：
10.1002/bit.20025
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发表时间：
2004-03-30
影响因子：
3.8
通讯作者：
Ai-Rubeai, M
中科院分区：
文献类型：
--
作者：
Bi, JX;Shuttleworth, J;Ai-Rubeai, M
中国仓鼠卵巢细胞被设计成诱导过表达p21（CIP1）周期蛋白依赖性激酶抑制剂，以实现细胞周期阻滞和提高细胞生产力。在p21（CIP1）阻滞的细胞中，稳定整合的IgG4基因产生的抗体增加了大约四倍。通过测量一系列细胞和代谢参数，研究了提高生产力的潜在生理基础。有趣的是，停滞细胞的平均细胞体积大约是增殖细胞的四倍。这伴随着线粒体质量、线粒体活性和核糖体蛋白S6水平的显著增加。我们的研究结果表明，p21（CIP1）诱导的细胞周期阻滞从细胞周期进程中解偶联细胞生长，并为如何在通常用于大规模生产药用蛋白的细胞系中实现提高生产力提供了新的见解。(C) 2004 Wiley期刊有限公司
Chinese hamster ovary cells have c been engineered to inducibly over-express the p21(CIP1) cyclin-dependent kinase inhibitor, to achieve cell cycle arrest and increase cell productivity. In p21(CIP1)-arrested cells production of antibody from a stably integrated IgG4 gene, was enhanced approximately fourfold. The underlying physiological basis for enhanced productivity was investigated by measuring a range of cellular and metabolic parameters. Interestingly, the average cell volume of arrested cells was approximately fourfold greater than that of proliferating cells. This was accompanied by significant increases in mitochondrial mass, mitochondrial activity, and ribosomal protein S6 levels. Our results suggest that p21(CIP1)-induced cell cycle arrest uncouples cell growth from cell-cycle progression, and provides new insight into how improved productivity can be achieved in a cell line commonly used for large-scale production of pharmaceutical proteins. (C) 2004 Wiley Periodicals, Inc.