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.
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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
Gardner MB (1994) Retroviruses and wild mice: an historical and personal retrospective view. Adv Cancer Res 65:169–201
Bittner JJ (1942) The milk influence of breast tumor in mice. Science 95:462–463
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
Schlom J, Spiegelman S, Moore D (1971) RNA-dependent DNA polymerase activity in virus-like particles isolated from human milk. Nature 231:97–100
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
Gardner M (2008) Search for oncogenic retroviruses in wild mice and man: historical reflections. Cancer Ther 6:285–302
Ford C (2004) Human MMTV-like virus (HMLV) and the viral aetiology of breast cancer. PhD Thesis, University of New South Wales, Sydney
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
Lawson JS, Heads J, Glenn WK, Whitaker NJ (2007) Breast feeding, breast milk and viruses. BMC Women’s Health 7:7–17
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
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
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
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
Teo IA, Shaunak S (1995) Polymerase chain reaction in situ: an appraisal of an emerging technique. Histochem J 27:647–659
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
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
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
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
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
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
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
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)
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
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
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
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
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
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
Nandi S, McGrath CM (1973) Mammary neoplasia in mice. Adv Cancer Res 17:353–414
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
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.
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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
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DOI: https://doi.org/10.1007/s10549-011-1421-6