Breast Cancer Research and Treatment

, Volume 129, Issue 1, pp 149–155 | Cite as

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

  • Harpreet Johal
  • Caroline Ford
  • Wendy Glenn
  • Joy Heads
  • James Lawson
  • William Rawlinson
Epidemiology

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.

Keywords

Mouse mammary tumor virus MMTV MMTV-like virus Envelope protein Hormonal influence PCR 

References

  1. 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 70:3576–3585PubMedCrossRefGoogle Scholar
  2. 2.
    Gardner MB (1994) Retroviruses and wild mice: an historical and personal retrospective view. Adv Cancer Res 65:169–201PubMedCrossRefGoogle Scholar
  3. 3.
    Bittner JJ (1942) The milk influence of breast tumor in mice. Science 95:462–463PubMedCrossRefGoogle Scholar
  4. 4.
    Moore D, Sarkar NH, Kramarsky B, Lasfargues EY, Charney J (1971) Some aspects of the search for a human mammary tumor virus. Cancer 28:1415–1424CrossRefGoogle Scholar
  5. 5.
    Schlom J, Spiegelman S, Moore D (1971) RNA-dependent DNA polymerase activity in virus-like particles isolated from human milk. Nature 231:97–100PubMedCrossRefGoogle Scholar
  6. 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 77:1301–1305PubMedCrossRefGoogle Scholar
  7. 7.
    Gardner M (2008) Search for oncogenic retroviruses in wild mice and man: historical reflections. Cancer Ther 6:285–302Google Scholar
  8. 8.
    Ford C (2004) Human MMTV-like virus (HMLV) and the viral aetiology of breast cancer. PhD Thesis, University of New South Wales, SydneyGoogle Scholar
  9. 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 360:187–195CrossRefGoogle Scholar
  10. 10.
    Lawson JS, Heads J, Glenn WK, Whitaker NJ (2007) Breast feeding, breast milk and viruses. BMC Women’s Health 7:7–17CrossRefGoogle Scholar
  11. 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 369:1107–1116PubMedCrossRefGoogle Scholar
  12. 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 55:5173–5179PubMedGoogle Scholar
  13. 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 60:589–598PubMedGoogle Scholar
  14. 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 61:1754–1759PubMedGoogle Scholar
  15. 15.
    Teo IA, Shaunak S (1995) Polymerase chain reaction in situ: an appraisal of an emerging technique. Histochem J 27:647–659PubMedGoogle Scholar
  16. 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 50:548–554PubMedCrossRefGoogle Scholar
  17. 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 43:668–674PubMedGoogle Scholar
  18. 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 22:4673–4680PubMedCrossRefGoogle Scholar
  19. 19.
    Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599PubMedCrossRefGoogle Scholar
  20. 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 10:7284–7289PubMedCrossRefGoogle Scholar
  21. 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 44:2155–2162PubMedGoogle Scholar
  22. 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 9:1118–1120PubMedGoogle Scholar
  23. 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)PubMedCrossRefGoogle Scholar
  24. 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 318:393–404CrossRefGoogle Scholar
  25. 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):233–236PubMedCrossRefGoogle Scholar
  26. 26.
    Smith MM, Kuhn L (2000) Exclusive breast feeding: does it have the potential to reduce breast feeding transmission of HIV-1? Nutr Rev 58:333–340PubMedCrossRefGoogle Scholar
  27. 27.
    Ho FC, Wong RL, Lawton JW (1979) Human colostral and breast milk cells. A light and electron microscopic study. Acta Paediatr Scand 68:389–396PubMedCrossRefGoogle Scholar
  28. 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 31:2603–2611PubMedCrossRefGoogle Scholar
  29. 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 161:2375–2382PubMedGoogle Scholar
  30. 30.
    Nandi S, McGrath CM (1973) Mammary neoplasia in mice. Adv Cancer Res 17:353–414CrossRefGoogle Scholar
  31. 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 123:2950–2954PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Harpreet Johal
    • 1
    • 2
  • Caroline Ford
    • 3
  • Wendy Glenn
    • 2
  • Joy Heads
    • 4
  • James Lawson
    • 2
  • William Rawlinson
    • 1
    • 2
    • 5
  1. 1.Virology Division, SEALS MicrobiologyPrince of Wales HospitalRandwickAustralia
  2. 2.School of Biotechnology and Biomolecular Sciences, Faculty of ScienceUniversity of New South Wales (UNSW)SydneyAustralia
  3. 3.Integrated Cancer Research Group, Prince of Wales Clinical School, Faculty of MedicineUniversity of New South WalesKensingtonAustralia
  4. 4.Royal Hospital for WomenRandwickAustralia
  5. 5.School of Medical Sciences, Faculty of MedicineUniversity of New South WalesKensingtonAustralia

Personalised recommendations