cMyc increases cell number through uncoupling of cell division from cell size in CHO cells
Open accessAbstract
BACKGROUND: Over the past decades, the increase in maximal cell numbers for the production of mammalian derived biologics has been in a large part due to the development of optimal feeding strategies. Engineering of the cell line is one of probable approaches for increasing cell numbers in bioreactor. RESULTS: We have demonstrated that the over-expression of the c-myc gene in immortalised CHO cells can increase proliferation rate and maximal cell density in batch culture compared to the control. The changes were attributed to a rapid transition into S-phase from a shortened duration of G1 phase and to the uncoupling of cell size from cell proliferation. To achieve the >70% increase in maximal cell density without additional supply of nutrients the cells underwent an overall reduction of 14% in size as well as a significant decrease in glucose and amino acid consumption rate. Consequently, the total biomass accumulation did not show a significant change from the control. The amount of hSEAP-hFc activity of the over expressing c-myc cell line was found to be within 0.7% of the control. CONCLUSION: It is shown that the manipulation of cell cycle kinetics and indirectly cell metabolism gives higher cell densities in CHO batch cultures. The unaltered apoptotic rate supported the proposition that the increase in cell number was a result of enhance cell cycle kinetics and cellular metabolism rather than increasing viability. Production of hSEAP-hFc from a constitutive c-myc over-expressing cell line did not increase with the increase in cell number.
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Cell cycle progression was faster when using c-myc oncogene in CHO cells.
“Cell cycle progression was also faster when using c-myc oncogene in CHO cells (Kuystermans and Al-Rubeai, 2009).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Kuystermans and Al-Rubeai, 2009
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Cited by
Sorted by citations
Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
- Authors
- Kuystermans, D., & Al-Rubeai, M.
- Affiliations
- University College Dublin (IE)
- Venue
- BMC Biotechnology
- Published
- 2009
- Volume
- 9
- Issue
- 1
- Pages
- 76
- ISSN
- 1472-6750 (ISSN-L)
- PMC
- PMC2749834
- OpenAlex
- W2066519212
- Cited by
- 33
- References
- 1
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Science Foundation Ireland
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- MYC overexpression, CHO cells, cell density, cell proliferation, cell cycle kinetics, cell size, glucose utilization, amino acid intake, cellular metabolism, recombinant protein expression, batch culture
- MeSH terms
- Amino Acids, Animals, Cell Count, Cell Division, Cricetulus, Culture Media, Glucose, Cricetinae, G1 Phase, Proto-Oncogene Proteins c-myc, CHO Cells, Apoptosis, Cell Culture Techniques, Bioreactors, Cell Size, Cell Proliferation
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