title: Regulation of cell cycle and productivity in NS0 cells by the over-expression of p21CIP1.
abstract: We have constructed NS0 myeloma cell lines that inducibly express the p21CIP1 cyclin dependent kinase inhibitor, using the Lacswitch system. Ectopic p21(CIP1) protein expression was rapidly induced within 12 h of addition of IPTG, causing G1-phase arrest and almost complete inhibition of cell proliferation. The production of a chimeric IgG4 antibody, expressed constitutively from an independent promoter, was found to be significantly increased by more than 4-fold in p21CIP1-arrested cells. This study demonstrates for the first time the successful construction of anchorage-independent and proliferation-controlled NS0 cell lines with enhanced secreted chimeric antibody production independent of the inducible promoter activity used to achieve cytostasis.
authors.affiliation: School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Shikiko
authors.initials: S
authors.lastname: Watanabe
authors.forename: John
authors.initials: J
authors.lastname: Shuttleworth
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Rubeai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015153:Blotting, Western / Q000379:methods; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D018844:Cyclin-Dependent Kinases