p27Kip1-mediated controlled proliferation technology increases constitutive sICAM production in CHO-DUKX adapted for growth in suspension and serum-free media.

Abstract	We have engineered dihydrofolate reductase-deficient (dhfr(-)) Chinese hamster ovary (CHO)-DUKX B11 cells adapted for growth in serum-free suspension cultures for unlinked muristerone-inducible expression of the cyclin-dependent kinase inhibitor p27Kip1 and constitutive expression of the soluble intercellular adhesion molecule-1 (sICAM), a potent common cold therapeutic. Conditional overexpression of p27Kip1 resulted in a sustained G1-specific growth arrest of transgenic CHO-DUKX associated with up to fivefold-increased specific sICAM productivity. Herein we exemplify the implementation of controlled proliferation technology in a major biopharmaceutical production cell line that is compatible with key requirements for large-scale production procedures, including constitutive transgene expression and anchorage-independent growth in serum-free media.
Authors	Heiko Meents, Barbara Enenkel, Rolf G Werner, Martin Fussenegger
Journal	Biotechnology and bioengineering (Biotechnol Bioeng) Vol. 79 Issue 6 Pg. 619-27 (Sep 20 2002) ISSN: 0006-3592 [Print] United States
PMID	12209809 (Publication Type: Comparative Study, Journal Article)
Copyright	Copyright 2002 Wiley Periodicals, Inc.
Chemical References	Cell Cycle Proteins Culture Media, Serum-Free Enzyme Inhibitors Suspensions Tumor Suppressor Proteins Intercellular Adhesion Molecule-1 Cyclin-Dependent Kinase Inhibitor p27 muristerone A Ecdysterone Tetrahydrofolate Dehydrogenase
Topics	Animals CHO Cells (physiology) Cell Culture Techniques (methods) Cell Cycle Proteins (biosynthesis, drug effects, genetics) Cell Division (drug effects, genetics) Cell Line Cricetinae Culture Media, Serum-Free Cyclin-Dependent Kinase Inhibitor p27 Dose-Response Relationship, Drug Ecdysterone (administration & dosage, analogs & derivatives) Enzyme Inhibitors Gene Expression Regulation (drug effects) Intercellular Adhesion Molecule-1 (biosynthesis, genetics) Protein Engineering Reproducibility of Results Sensitivity and Specificity Suspensions Tetrahydrofolate Dehydrogenase (genetics) Tumor Suppressor Proteins (biosynthesis, drug effects, genetics)

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