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Cited by 58Viral Infectious Diseases and Gene Expression in InsectsCancer-related Molecular PathwaysFungal and yeast genetics research

Enhancement of cell proliferation in various mammalian cell lines by gene insertion of a cyclin-dependent kinase homolog

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Jaluria, Pratik, Betenbaugh, Michael, Konstantopoulos, Konstantinos, Shiloach, Joseph·2007·BMC Biotechnology
DOI 10.1186/1472-6750-7-71PMC PMC2164945
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Abstract

Background: Genomics tools, particularly DNA microarrays, have found application in a number of areas including gene discovery and disease characterization. Despite the vast utility of these tools, little work has been done to explore the basis of distinct cellular properties, especially those important to biotechnology such as growth. And so, with the intent of engineering cell lines by manipulating the expression of these genes, anchorage-independent and anchorage-dependent HeLa cells, displaying markedly different growth characteristics, were analyzed using DNA microarrays. Results: Two genes, cyclin-dependent kinase like 3 (cdkl3) and cytochrome c oxidase subunit (cox15), were up-regulated in the faster growing, anchorage-independent (suspension) HeLa cells relative to the slower growing, anchorage-dependent (attached) HeLa cells. Enhanced expression of either gene in the attached HeLa cells resulted in elevated cell proliferation, though insertion of cdkl3 had a greater impact than that of cox15. Moreover, flow cytometric analysis indicated that cells with an insert of cdkl3 were able to transition from the G0/G1 phases to the S phase faster than control cells. In turn, expression of cox15 was seen to increase the maximum viable cell numbers achieved relative to the control, and to a greater extent than cdkl3. Quantitatively similar results were obtained with two Human Embryonic Kidney-293 (HEK-293) cell lines and a Chinese Hamster Ovary (CHO) cell line. Additionally, HEK-293 cells secreting adipocyte complement-related protein of 30 kDa (acrp30) exhibited a slight increase in specific protein production and higher total protein production in response to the insertion of either cdkl3 or cox15. Conclusion: These results are consistent with previous studies on the functionalities of cdkl3 and cox15. For instance, the effect of cdkl3 on cell growth is consistent with its homology to the cdk3 gene which is involved in G1 to S phase transition. Likewise, the increase in cell viability due to cox15 expression is consistent with its role in oxidative phosphorylation as an assembly factor for cytochrome c oxidase and its involvement removing apoptosis-inducing oxygen radicals. Collectively, the present study illustrates the potential of using microarray technology to identify genes influential to specific cellular processes with the possibility of engineering cell lines as desired to meet production needs.

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  • CDKL3 gene insertion accelerates cell proliferation of 293 and CHO cells.

    “The CDKL3 gene insertion also accelerates cell proliferation of 293 and CHO cells (Jaluria et al., 2007).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Jaluria et al., 2007

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Cited by

Sorted by citations

Authors
Jaluria, P., Betenbaugh, M., Konstantopoulos, K., & Shiloach, J.
Affiliations
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
Corresponding author
Shiloach, Joseph
ORCID
Venue
BMC Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2007-10-18
Volume
7
Issue
1
Pages
71-71
ISSN
1472-6750 (ISSN-L)
DOI
10.1186/1472-6750-7-71
PMC
PMC2164945
OpenAlex
W2026650987
Cited by
58
References
2
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 4 · 2015: 3 · 2014: 2 · 2013: 4
FWCI
0.80
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Biotechnology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Yeshiva University
  • National Institutes of Health
  • Albert Einstein College of Medicine, Yeshiva University
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR053358)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
cytochrome c oxidase subunits, cell proliferation, anchorage-independent growth, HeLa cells, G1/S transition, cell viability, cell line engineering, HEK293 cells, CHO cells, adiponectin, recombinant protein expression
MeSH terms
Animals, Cell Adhesion, Cell Count, Cell Survival, Contact Inhibition, Cricetulus, Electron Transport Complex IV, Female, Cricetinae, HeLa Cells, Humans, Interphase, Phenotype, Up-Regulation, CHO Cells, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinases, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cell Proliferation

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