The relationship between mTOR signalling pathway and recombinant antibody productivity in CHO cell lines

Hdl Handle:
http://hdl.handle.net/10147/313533
Title:
The relationship between mTOR signalling pathway and recombinant antibody productivity in CHO cell lines
Authors:
Edros, Raihana; McDonnell, Susan; Al-Rubeai, Mohamed
Citation:
BMC Biotechnology. 2014 Feb 17;14(1):15
Issue Date:
17-Feb-2014
URI:
http://dx.doi.org/10.1186/1472-6750-14-15; http://hdl.handle.net/10147/313533
Abstract:
Abstract 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.
Local subject classification:
BIOTECHNOLOGY

Full metadata record

DC FieldValue Language
dc.contributor.authorEdros, Raihanaen_GB
dc.contributor.authorMcDonnell, Susanen_GB
dc.contributor.authorAl-Rubeai, Mohameden_GB
dc.date.accessioned2014-02-28T16:16:22Z-
dc.date.available2014-02-28T16:16:22Z-
dc.date.issued2014-02-17-
dc.identifier.citationBMC Biotechnology. 2014 Feb 17;14(1):15en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/1472-6750-14-15-
dc.identifier.urihttp://hdl.handle.net/10147/313533-
dc.description.abstractAbstract 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.-
dc.subject.otherBIOTECHNOLOGYen_GB
dc.titleThe relationship between mTOR signalling pathway and recombinant antibody productivity in CHO cell linesen_GB
dc.language.rfc3066en-
dc.rights.holderRaihana Edros et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-02-28T12:55:28Z-
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