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首页> 外文期刊>BMC Biotechnology >The relationship between mTOR signalling pathway and recombinant antibody productivity in CHO cell lines
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The relationship between mTOR signalling pathway and recombinant antibody productivity in CHO cell lines

机译：CHO细胞系中mTOR信号通路与重组抗体生产力之间的关系

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Background High recombinant protein productivity in mammalian cell lines is often associated with phenotypic changes in protein content, energy metabolism, and cell growth, but the key determinants that regulate productivity are still not clearly understood. The mammalian target of rapamycin (mTOR) signalling pathway has emerged as a central regulator for many cellular processes including cell growth, apoptosis, metabolism, and protein synthesis. This role of this pathway changes in response to diverse environmental cues and allows the upstream proteins that respond directly to extracellular signals (such as nutrient availability, energy status, and physical stresses) to communicate with downstream effectors which, in turn, regulate various essential cellular processes. Results In this study, we have performed a transcriptomic analysis using a pathway-focused polymerase chain reaction (PCR) array to compare the expression of 84 target genes related to the mTOR signalling in two recombinant CHO cell lines with a 17.4-fold difference in specific monoclonal antibody productivity ( q p ). Eight differentially expressed genes that exhibited more than a 1.5-fold change were identified. Pik3cd (encoding the Class 1A catalytic subunit of phosphatidylinositol 3-kinase [PI3K]) was the most differentially expressed gene having a 71.3-fold higher level of expression in the high producer cell line than in the low producer. The difference in the gene’s transcription levels was confirmed at the protein level by examining expression of p110δ. Conclusion Expression of p110δ correlated with specific productivity ( q p ) across six different CHO cell lines, with a range of expression levels from 3 to 51?pg/cell/day, suggesting that p110δ may be a key factor in regulating productivity in recombinant cell lines.
机译：背景技术哺乳动物细胞系中重组蛋白的高生产率通常与蛋白含量，能量代谢和细胞生长的表型变化有关，但调节生产率的关键决定因素仍不清楚。雷帕霉素（mTOR）信号转导途径的哺乳动物靶点已成为许多细胞过程（包括细胞生长，凋亡，代谢和蛋白质合成）的中央调节剂。该途径的这种作用会响应各种环境提示而发生变化，并使直接对细胞外信号（例如营养素供应，能量状态和身体压力）直接响应的上游蛋白质与下游效应器进行通讯，进而调节各种必需的细胞流程。结果在这项研究中，我们使用了以途径为重点的聚合酶链反应（PCR）阵列进行了转录组学分析，比较了与两种mTOR信号转导相关的84个靶基因在两种重组CHO细胞系中的表达，其特异性差异为17.4倍。单克隆抗体生产率（q p ）。确定了八个差异表达基因，它们表现出超过1.5倍的变化。 Pik3cd（编码磷脂酰肌醇3-激酶[PI3K]的1A类催化亚基）是差异最大的基因，其高水平生产者细胞系的表达水平比低水平生产者高71.3倍。通过检查p110δ的表达，在蛋白质水平上证实了基因转录水平的差异。结论在6种不同的CHO细胞系中，p110δ的表达与单位生产力（q p ）相关，表达水平范围为3至51？pg / cell / day，这表明p110δ可能是关键调节重组细胞系生产力的因素。

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