Skip to main content

Advertisement

Log in

Mouse mammary tumor like virus sequences in breast milk from healthy lactating women

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Mouse mammary tumor virus (MMTV) has been a long standing candidate as a potential cause of some human breast cancers. Forty years ago, electron microscopic images of MMTV-like particles were identified in milk from 5% of healthy lactating women. These observations, however, have not been confirmed by modern methods. The purpose of this study was to confirm the presence of MMTV-like DNA sequences in human milk from normal lactating women. Standard and in situ PCR analyses were conducted on DNA extracted from fresh breast milk samples collected from a group of 91 healthy lactating women volunteers. The MMTV-like viral positive PCR products were sequenced and a phylogenetic tree was constructed to compare these sequences. Immunohistochemistry analyses were performed on breast milk cells using polyclonal rabbit antibodies against affinity-purified MMTV envelope glycoproteins 52/36. MMTV-like envelope gene sequences were identified by PCR in 5% (4/91) of breast milk samples from healthy lactating women volunteers. These observations were confirmed by in situ PCR and immunohistochemistry using MMTV gp52/36 antibodies. These findings confirm the presence of MMTV-like gene sequences in human milk. As MMTV is transmitted via milk from mouse mothers to their newborn pups to cause mammary tumors when they become adults, this indicates a means of transmission of this virus in humans.

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

Access this article

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

Similar content being viewed by others

References

  1. Lawson JS, Glenn WK, Salmons B, Ye Y, Heng B, Moody P, Johal H, Rawlinson WD, Delprado W, Lutze-Mann L et al (2010) Mouse mammary tumor virus-like sequences virus and human breast cancer. Cancer Res 70:3576–3585

    Article  PubMed  CAS  Google Scholar 

  2. Gardner MB (1994) Retroviruses and wild mice: an historical and personal retrospective view. Adv Cancer Res 65:169–201

    Article  PubMed  CAS  Google Scholar 

  3. Bittner JJ (1942) The milk influence of breast tumor in mice. Science 95:462–463

    Article  PubMed  CAS  Google Scholar 

  4. Moore D, Sarkar NH, Kramarsky B, Lasfargues EY, Charney J (1971) Some aspects of the search for a human mammary tumor virus. Cancer 28:1415–1424

    Article  Google Scholar 

  5. Schlom J, Spiegelman S, Moore D (1971) RNA-dependent DNA polymerase activity in virus-like particles isolated from human milk. Nature 231:97–100

    Article  PubMed  CAS  Google Scholar 

  6. Dion AS, Farwell DC, Pomenti AA, Girardi AJ (1980) A human protein related to the major envelope protein of murine mammary tumor virus: identification and characterization. Proc Natl Acad Sci USA 77:1301–1305

    Article  PubMed  CAS  Google Scholar 

  7. Gardner M (2008) Search for oncogenic retroviruses in wild mice and man: historical reflections. Cancer Ther 6:285–302

    CAS  Google Scholar 

  8. Ford C (2004) Human MMTV-like virus (HMLV) and the viral aetiology of breast cancer. PhD Thesis, University of New South Wales, Sydney

  9. Beral V, Bull D, Doll D, Peto R, Reeves G (2002) Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 360:187–195

    Article  Google Scholar 

  10. Lawson JS, Heads J, Glenn WK, Whitaker NJ (2007) Breast feeding, breast milk and viruses. BMC Women’s Health 7:7–17

    Article  Google Scholar 

  11. Coovadia HM, Rollins NC, Bland RM, Little K, Coutsoudis A, Bennish ML, Newell ML (2007) Mother-to-child transmission of HIV-1 during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 369:1107–1116

    Article  PubMed  Google Scholar 

  12. Wang Y, Holland JF, Bleiweiss IJ, Melana SM, Liu X, Pelisson I, Cantarella A, Stellrecht K, Mani S, Pogo BG-T (1995) Detection of mammary tumor virus env gene-like sequences in human breast cancer. Cancer Res 55:5173–5179

    PubMed  CAS  Google Scholar 

  13. Ono M, Yasunaga T, Miyata T, Ushikubo H (1986) Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. J Virol 60:589–598

    PubMed  CAS  Google Scholar 

  14. Liu B, Wang Y, Melana SM, Pelisson I, Najfeld V, Holland JF, Pogo BG (2001) Identification of a proviral structure in human breast cancer. Cancer Res 61:1754–1759

    PubMed  CAS  Google Scholar 

  15. Teo IA, Shaunak S (1995) Polymerase chain reaction in situ: an appraisal of an emerging technique. Histochem J 27:647–659

    PubMed  CAS  Google Scholar 

  16. Johal H, Scott GM, Jones R, Camaris C, Riordan S, Rawlinson WD (2009) Mouse mammary tumour virus-like virus (MMTV-LV) is present within the liver in a wide range of hepatic disorders and unrelated to nuclear p53 expression or hepatocarcinogenesis. J Hepatol 50:548–554

    Article  PubMed  CAS  Google Scholar 

  17. Faedo M, Hinds LA, Singleton GR, Rawlinson WD (2007) Prevalence of mouse mammary tumor virus (MMTV) in wild mice (mus musculus) in southeastern Australia. J Wildl Dis 43:668–674

    PubMed  CAS  Google Scholar 

  18. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    Article  PubMed  CAS  Google Scholar 

  19. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  20. Ford CE, Faedo M, Rawlinson WD (2004) Mouse mammary tumor virus-like RNA transcripts and DNA are found in affected cells of human breast cancer. Clin Cancer Res 10:7284–7289

    Article  PubMed  CAS  Google Scholar 

  21. Slagle L, Lanford RE, Medina D, Butel JS (1984) Expression of mammary tumor virus proteins in preneoplastic outgrowth lines and mammary tumors of BALB/cV mice. Cancer Res 44:2155–2162

    PubMed  CAS  Google Scholar 

  22. Ford CE, Tran D, Deng Y, Ta VT, Rawlinson WD, Lawson JS (2003) Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women. Clin Cancer Res 9:1118–1120

    PubMed  CAS  Google Scholar 

  23. Hareuveni M, Lathe R (1990) Breast cancer sequences identified by mouse mammary tumour virus (MMTV) antiserum are unrelated to MMTV. Int J Cancer 46:1134–1135 (Letter to the Editor)

    Article  PubMed  CAS  Google Scholar 

  24. Mant C, Gillett C, Arrigo CD, Cason J (2004) Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies. J Virol 318:393–404

    Article  CAS  Google Scholar 

  25. Wang Y, Melana SM, Baker B, Bleiweiss IJ, Fernandez-Cobo M, Mandeli JF, Holland JF, Pogo BG-T (2003) High prevalence of MMTV-like env gene sequences in gestational breast cancer. Med Oncol 20(3):233–236

    Article  PubMed  CAS  Google Scholar 

  26. Smith MM, Kuhn L (2000) Exclusive breast feeding: does it have the potential to reduce breast feeding transmission of HIV-1? Nutr Rev 58:333–340

    Article  PubMed  CAS  Google Scholar 

  27. Ho FC, Wong RL, Lawton JW (1979) Human colostral and breast milk cells. A light and electron microscopic study. Acta Paediatr Scand 68:389–396

    Article  PubMed  CAS  Google Scholar 

  28. Finke D, Acha-Orbea H (2001) Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs. Eur J Immunol 31:2603–2611

    Article  PubMed  CAS  Google Scholar 

  29. Golovkina TV, Dudley JP, Ross SR (1998) B and T cells are required for mouse mammary tumour virus spread within the mammary gland. J Immunol 161:2375–2382

    PubMed  CAS  Google Scholar 

  30. Nandi S, McGrath CM (1973) Mammary neoplasia in mice. Adv Cancer Res 17:353–414

    Article  Google Scholar 

  31. Couto E, Banks E, Reeves G, Pirie K, Beral V (2008) Family history and breast cancer tumour characteristics in screened women. Int J Cancer 123:2950–2954

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Dinh Tran from St. Vincent’s Hospital for his help in the cell marker staining performed in this study.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James Lawson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Johal, H., Ford, C., Glenn, W. et al. Mouse mammary tumor like virus sequences in breast milk from healthy lactating women. Breast Cancer Res Treat 129, 149–155 (2011). https://doi.org/10.1007/s10549-011-1421-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-011-1421-6

Keywords

Navigation