Skip to main content

Advertisement

SpringerLink
Log in

Construction of a recombinant human FGF1 expression vector for mammary gland-specific expression in human breast cancer cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Human Fibroblast growth factor 1 (FGF1) has been recognized as a valuable protein drug for the treatment of many diseases because of its multiple functions in regulating a variety of biological processes involved in embryonic development, cell growth and differentiation, morphogenesis, tissue repair, and others. The aim of this study was to develop an FGF1 mammary gland-specific expression vector to produce FGF1 on a large scale from transgenic cows to meet the demand for FGF1 in medical use. In this study, we generated an FGF1 mammary gland-specific expression vector and validated its function in human MCF-7 cells. This vector was shown to successfully express functional FGF1, thus potentially enabling the generation of transgenic cows to be used as mammary gland bioreactors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Itoh N, Ornitz DM (2004) Evolution of the FGF and FGFR gene families. Trends Genet 20:563–569

    Article  CAS  PubMed  Google Scholar 

  2. Shing Y, Folkman J, Sullivan R, Butterfield C, Murray J, Klagsbrun M (1984) Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science 223:1296–1299

    Article  CAS  PubMed  Google Scholar 

  3. Wiedlocha A (1999) Activation of the cell proliferation program by acidic fibroblast growth factor (aFGF). Postepy Hig Med Dosw 53:277–289

    CAS  PubMed  Google Scholar 

  4. Burgess WH, Maciag T (1989) The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem 58:575–606

    Article  CAS  PubMed  Google Scholar 

  5. Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2:REVIEWS3005-1

    Article  Google Scholar 

  6. Martin GR (1998) The roles of FGFs in the early development of vertebrate limbs. Genes Dev 12:1571–1586

    Article  CAS  PubMed  Google Scholar 

  7. Chen CW, Liu CS, Chiu IM et al (2010) The signals of FGFs on the neurogenesis of embryonic stem cells. J Biomed Sci 17:33

    Article  PubMed  Google Scholar 

  8. Basilico C, Moscatelli D (1992) The FGF family of growth factors and oncogenes. Adv Cancer Res 59:115–165

    Article  CAS  PubMed  Google Scholar 

  9. Naski MC, Ornitz DM (1998) FGF signaling in skeletal development. Front Biosci 3:d781–d794

    CAS  PubMed  Google Scholar 

  10. Rosengart TK, Budenbender KT, Duenas M, Mack CA, Zhang QX, Isom OW (1997) Therapeutic angiogenesis: a comparative study of the angiogenic potential of acidic fibroblast growth factor and heparin. J Vasc Surg 26:302–312

    Article  CAS  PubMed  Google Scholar 

  11. Buehler A, Martire A, Strohm C et al (2002) Angiogenesis-independent cardioprotection in FGF-1 transgenic mice. Cardiovasc Res 55:768–777

    Article  CAS  PubMed  Google Scholar 

  12. Cuevas P, Carceller F, Martinez-Coso V et al (1999) Cardioprotection from ischemia by fibroblast growth factor: role of inducible nitric oxide synthase. Eur J Med Res 4:517–524

    CAS  PubMed  Google Scholar 

  13. Everall IP, Trillo-Pazos G, Bell C, Mallory M, Sanders V, Masliah E (2001) Amelioration of neurotoxic effects of HIV envelope protein gp120 by fibroblast growth factor: a strategy for neuroprotection. J Neuropathol Exp Neurol 60:293–301

    CAS  PubMed  Google Scholar 

  14. Guo F, Gopaul DN, van Duyne GD (1997) Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse. Nature 389:40–46

    Article  CAS  PubMed  Google Scholar 

  15. Metzger D, Feil R (1999) Engineering the mouse genome by site-specific recombination. Curr Opin Biotechnol 10:470–476

    Article  CAS  PubMed  Google Scholar 

  16. Schmidt EE, Taylor DS, Prigge JR, Barnett S, Capecchi MR (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc Natl Acad Sci USA 97:13702–13707

    Article  CAS  PubMed  Google Scholar 

  17. Dale EC, Ow DW (1991) Gene transfer with subsequent removal of the selection gene from the host genome. Proc Natl Acad Sci USA 88:10558–10562

    Article  CAS  PubMed  Google Scholar 

  18. Russell SH, Hoopes JL, Odell JT (1992) Directed excision of a transgene from the plant genome. Mol Gen Genet 234:49–59

    CAS  PubMed  Google Scholar 

  19. Hare PD, Chua NH (2002) Excision of selectable marker genes from transgenic plants. Nat Biotechnol 20:575–580

    Article  CAS  PubMed  Google Scholar 

  20. Langer SJ, Ghafoori AP, Byrd M, Leinwand L (2002) A genetic screen identifies novel non-compatible loxP sites. Nucleic Acids Res 30:3067–3077

    Article  CAS  PubMed  Google Scholar 

  21. Bethke B, Sauer B (1997) Segmental genomic replacement by Cre-mediated recombination: genotoxic stress activation of the p53 promoter in single-copy transformants. Nucleic Acids Res 25:2828–2834

    Article  CAS  PubMed  Google Scholar 

  22. Araki K, Araki M, Yamamura K (2002) Site-directed integration of the cre gene mediated by Cre recombinase using a combination of mutant lox sites. Nucleic Acids Res 30:e103

    Article  PubMed  Google Scholar 

  23. Araki K, Araki M, Yamamura K (2006) Negative selection with the diphtheria toxin A fragment gene improves frequency of Cre-mediated cassette exchange in ES cells. J Biochem 140:793–798

    Article  CAS  PubMed  Google Scholar 

  24. Shin JT, Opalenik SR, Wehby JN et al (1996) Serum-starvation induces the extracellular appearance of FGF-1. Biochim Biophys Acta 1312:27–38

    Article  PubMed  Google Scholar 

  25. Strydom DJ, Harper JW, Lobb RR (1986) Amino acid sequence of bovine brain derived class 1 heparin-binding growth factor. Biochemistry 25:945–951

    Article  CAS  PubMed  Google Scholar 

  26. Crumley G, Bellot F, Kaplow JM, Schlessinger J, Jaye M, Dionne CA (1991) High-affinity binding and activation of a truncated FGF receptor by both aFGF and bFGF. Oncogene 6:2255–2262

    CAS  PubMed  Google Scholar 

  27. Lozano RM, Pineda-Lucena A, Gonzalez C et al (2000) 1H NMR structural characterization of a nonmitogenic, vasodilatory, ischemia-protector and neuromodulatory acidic fibroblast growth factor. Biochemistry 39:4982–4993

    Article  CAS  PubMed  Google Scholar 

  28. Cuilliere ML, Tregoat V, Bene MC, Faure G, Montagne P (1999) Changes in the kappa-casein and beta-casein concentrations in human milk during lactation. J Clin Lab Anal 13:213–218

    Article  CAS  PubMed  Google Scholar 

  29. Kabotyanski EB, Huetter M, Xian W, Rijnkels M, Rosen JM (2006) Integration of prolactin and glucocorticoid signaling at the beta-casein promoter and enhancer by ordered recruitment of specific transcription factors and chromatin modifiers. Mol Endocrinol 20:2355–2368

    Article  CAS  PubMed  Google Scholar 

  30. Groner B, Gouilleux F (1995) Prolactin-mediated gene activation in mammary epithelial cells. Curr Opin Genet Dev 5:587–594

    Article  CAS  PubMed  Google Scholar 

  31. McManaman JL, Hanson L, Neville MC, Wright RM (2000) Lactogenic hormones regulate xanthine oxidoreductase and beta-casein levels in mammary epithelial cells by distinct mechanisms. Arch Biochem Biophys 373:318–327

    Article  CAS  PubMed  Google Scholar 

  32. Langle-Rouault F, Patzel V, Benavente A et al (1998) Up to 100-fold increase of apparent gene expression in the presence of Epstein-Barr virus oriP sequences and EBNA1: implications of the nuclear import of plasmids. J Virol 72:6181–6185

    CAS  PubMed  Google Scholar 

  33. Rawlins DR, Milman G, Hayward SD, Hayward GS (1985) Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell 42:859–868

    Article  CAS  PubMed  Google Scholar 

  34. Middleton T, Sugden B (1994) Retention of plasmid DNA in mammalian cells is enhanced by binding of the Epstein-Barr virus replication protein EBNA1. J Virol 68:4067–4071

    CAS  PubMed  Google Scholar 

  35. Kirchmaier AL, Sugden B (1995) Plasmid maintenance of derivatives of oriP of Epstein-Barr virus. J Virol 69:1280–1283

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the China National Foundation for Natural Science (13002104) to HO. All vectors constructed in this article are available from the authors upon request from academic researchers.

Author information

Authors and Affiliations

  1. Department of Animal Biotechnology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, Jilin, China

    Yang Zhou, Linzhu Ren, Jianguo Zhu, Sen Yan, Haijun Wang, Na Song, Li Li, Hongsheng Ouyang & Daxin Pang

Authors
  1. Yang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linzhu Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianguo Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sen Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haijun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Na Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hongsheng Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daxin Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hongsheng Ouyang or Daxin Pang.

Additional information

Yang Zhou and Linzhu Ren contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, Y., Ren, L., Zhu, J. et al. Construction of a recombinant human FGF1 expression vector for mammary gland-specific expression in human breast cancer cells. Mol Cell Biochem 354, 39–46 (2011). https://doi.org/10.1007/s11010-011-0803-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-0803-8

Keywords

Search

Navigation