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Production of Recombinant Human CSF–1 in an Inducible Mammalian Expression System


We describe the production of human colony stimulating factor–1 (CSF–1) in an inducible mammalian expression system that is capable of producing milligram quantities of recombinant protein. The system involves CV–1 derived cell lines that contain integrated copies of an SV40–origin–containing CSF–1 expression plasmid. SV40–T–antigen–dependent replication of the integrated expression plasmid was induced by infecting such cells with either SV40 or a defective recombinant adenovirus (Ad5.SVR3) encoding SV40 large T antigen. The transient increase in recombinant plasmid copy number resulted in high levels of CSF–1 expression. Induction by AD5.SVR3 gave ten–fold higher expression levels than induction with SV40. This intermediate–scale expression system provides an efficient method of producing a moderate level of recombinant protein following cDNA cloning.

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  1. Okayama, H. and Berg, P. 1982. High-efficiency cloning of full-length cDNA. Mol. Cell. Biol. 2:161–170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Okayama, H. and Berg, P. 1983. A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol. Cell. Biol. 3:280–289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gluzman, Y. 1981. SV40-transformed simian cells support the replication of early SV40 mutants. Cell 23:175–182.

    Article  CAS  PubMed  Google Scholar 

  4. Kawasaki, E.S., Ladner, M.B., Wang, A.M., VanArsdell, J., Warren, M.K., Coyne, M.Y., Schweickart, V.L., Lee, M.T., Wilson, K.J., Boosman, A., Stanley, E.R., Ralph, P., and Mark, D.F. 1985. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science 230:291–296.

    Article  CAS  PubMed  Google Scholar 

  5. Botchan, M., Topp, W. and Sambrook, J. 1979. Studies on SV40 excision from cellular chromosomes. Cold Spring Symp. Quant. Biol. 43:709–719.

    Article  CAS  Google Scholar 

  6. Gorman, C. Padmanabhan, R., and Howard, B. 1983. High efficiency DNA-mediated transformation of primate cells. Science 221:551–553.

    Article  CAS  PubMed  Google Scholar 

  7. Southern, P.J. and Berg, P. 1982. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J. Mol. Appl. Gen. 1:327–341.

    CAS  Google Scholar 

  8. Das, S.K., Stanley, E.R., Guilbert, L.J., and Forman, L.W. 1981. Human colony-stimulating factor (CSF-1) radioimmunoassay: resolution of three subclasses of human colony-stimulating factors. Blood 58:630–641.

    CAS  PubMed  Google Scholar 

  9. Wu, M., Cini, J.K., and Yunis, A.A. 1979. Purification of a colony-stimulating factor from cultured pancreatic carcinoma cells. J. Biol. Chem. 254:6226–6228.

    CAS  PubMed  Google Scholar 

  10. Ralph, P., Warren, M.K., Lee, M.-T., Csejtey, J., Weaver, J.F., Broxmeyer, H.E., Williams, D.E., Stanley, E.R., and Kawasaki, E.S. 1986. Inducible production of human macrophage growth factor, CSF-1. Blood 68:633–639.

    CAS  PubMed  Google Scholar 

  11. Metcalf, D. 1970. Studies on colony formation in vitro by mouse bone marrow cells. II. Action of colony stimulating factor. J. Cell. Physiol. 76:89–99.

    Article  CAS  PubMed  Google Scholar 

  12. Stanley, E.R. 1981. Colony stimulating factors, p.101–132. In: The Lymphokines. Hadden, J.W. and Stewart II, W.E.(eds.) Humana Press, Clifton, NJ.

    Chapter  Google Scholar 

  13. Van Doren, K. and Gluzman, Y. 1984. Efficient transformation of human fibroblasts by adenovirus-simian virus 40 recombinants. Mol. Cell. Biol. 4:1653–1656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gluzman, Y., Frisque, R.J., and Sambrook, J. 1980. Origin-defective mutants of SV40. Cold Spring Harbor Symp. Quant. Biol. 44:293–300.

    Article  CAS  PubMed  Google Scholar 

  15. Gluzman, Y., Sambrook, J.F., and Frisque, R.J. 1980. Expression of early genes of origin-defective mutants of simian virus 40. Proc. Nat. Acad. Sci. USA 77:3898–3902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Graham, F.L., Smiley, J., Russell, W.C., and Nairn, R. 1977. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. 36:59–72.

    Article  CAS  PubMed  Google Scholar 

  17. Halenbeck, R., Shadle, P., Lee, P-J., Lee, M-T., and Nairn, R. 1988. Purification and characterization of recombinant human macrophage colony-stimulating factor and generation of a neutralizing antibody useful for Western analysis. Submitted.

  18. Ladner, M.B., Martin, G.A., Nobel, J.A., Nikoloff, D.M., Tal, R., Kawasaki, E.S., and White, T.J. 1987. Human CSF-1: gene structure and alternative splicing of mRNA precursors. EMBO J. 6:2693–2698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Beck, E., Ludwig, G., Auerswald, E.A., Reiss, B., and Schaller, H. 1982. Nucleotide sequence and exact localization of the neomycin phosphotransferase gene from transposon Tn5. Gene 19:327–336.

    Article  CAS  PubMed  Google Scholar 

  20. Maniatis, T., Fritsch, E.F., and Sambrook, J. 1982. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  21. Graham, F.L. and Van Der Eb, A.J. 1973. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456–467.

    Article  CAS  PubMed  Google Scholar 

  22. Jones, N. and Shenk, T. 1979. Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell 17:683–689.

    Article  CAS  PubMed  Google Scholar 

  23. Manos, M.M. and Gluzman, Y. 1984. Simian virus 40 large T-antigen point mutants that are defective in viral DNA replication but competent in oncogenic transformation. Mol. Cell. Biol. 4:1125–1133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stanley, E.R. 1985. The macrophage colony-stimulating factor, CSF-1. Methods in Immunology 116:564–587.

    CAS  Google Scholar 

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Weaver, J., McCormick, F. & Manos, M. Production of Recombinant Human CSF–1 in an Inducible Mammalian Expression System. Nat Biotechnol 6, 287–290 (1988).

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