Skip to main content

Advertisement

Springer Nature Link
Log in

MMTV Infectious Cycle and the Contribution of Virus-encoded Proteins to Transformation of Mammary Tissue

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Mouse mammary tumor virus has served as a major model for the study of breast cancer since its discovery 1920’s as a milk-transmitted agent. Much is known about in vivo infection by this virus, which initially occurs in lymphocytes that then carry virus to mammary tissue. In addition to the virion proteins, MMTV encodes a number of accessory proteins that facilitate high level in vivo infection. High level infection of lymphoid and mammary epithelial cells ensures efficient passage of virus to the next generation. Since MMTV causes mammary tumors by insertional activation of oncogenes, which is thought to be a stochastic process, mammary epithelial cell transformation is a by-product of the infectious cycle. The envelope protein may also participate in transformation. Although there have been several reports of a similar virus in human breast cancer, the existence of a human MTV has not been definitely established.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

Abbreviations

MMTV:

mouse mammary tumor virus

HMTV:

human mammary tumor virus

Sag:

superantigen

Env:

envelope

MLV:

murine leukemia virus

HIV-1:

human immunodeficiency virus-1

HTLVI:

human T cell leukemia virus I

CA:

capsid

NC:

nucleocapsid

LTR:

long terminal repeat

EIAV:

equine infectious anemia virus

SU:

surface

TM:

transmembrane

TfR1:

transferrin receptor 1

Rem:

regulator of export of MMTV

TLR4:

Toll-like receptor 4

DCs:

dendritic cells

ITAM:

immunoreceptor tyrosine-based activation motif

EBV:

Epstein Barr Virus

KSHV:

Kaposi’s Sarcoma Herpes Virus

CIS:

common integration site

fgf:

fibroblast growth factor

References

  1. Bittner JJ. Some possible effects of nursing on the mammary gland tumor incidence in mice. Science 1936;84:162. doi:10.1126/science.84.2172.162.

    Article  PubMed  Google Scholar 

  2. Nandi S, McGrath CM. Mammary neoplasia in mice. Adv Cancer Res. 1973;17:353–414. doi:10.1016/S0065-230X(08)60535-7.

    Article  Google Scholar 

  3. Ross SR. Using genetics to probe host–virus interactions: the mouse mammary tumor virus model. Microbes Infect. 2000;2:1215–23. doi:10.1016/S1286-4579(00)01275-2.

    Article  PubMed  CAS  Google Scholar 

  4. Mink S, Hartig E, Jennewein P, Doppler W, Cato ACB. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NF-1 and novel transcription factor, mammary cell-activating factor. Mol Cell Biol. 1992;11:4906–18.

    Google Scholar 

  5. Mok E, Golovkina TV, Ross SR. A mouse mammary tumor virus (MMTV) mammary gland enhancer confers tissue-specific, but not lactation-dependent expression in transgenic mice. J Virol. 1992;66:7529–32.

    PubMed  CAS  Google Scholar 

  6. Reuss FU, Coffin JM. Stimulation of mouse mammary tumor virus superantigen expression by an intragenic enhancer. Proc Natl Acad Sci U S A. 1995;92:9293–7. doi:10.1073/pnas.92.20.9293.

    Article  PubMed  CAS  Google Scholar 

  7. Zhu Q, Maitra U, Johnston D, Lozano M, Dudley JP. The homeodomain protein CDP regulates mammary-specific gene transcription and tumorigenesis. Mol Cell Biol. 2004;24:4810–23. doi:10.1128/MCB.24.11.4810-4823.2004.

    Article  PubMed  CAS  Google Scholar 

  8. Vicent GP, Ballare C, Zaurin R, Saragueta P, Beato M. Chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways. Ann N Y Acad Sci. 2006;1089:59–72. doi:10.1196/annals.1386.025.

    Article  PubMed  CAS  Google Scholar 

  9. Coffin JM, Hughes SH, Varmus HE, editors. Retroviruses. Cold Spring Harbor (NY): CSHL Press; 1997.

  10. Payne SL, Elder JH. The role of retroviral dUTPases in replication and virulence. Curr Protein Pept Sci. 2001;2:381–8. doi:10.2174/1389203013381008.

    Article  PubMed  CAS  Google Scholar 

  11. Ross SR, Schofield JJ, Farr CJ, Bucan M. Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus. Proc Natl Acad Sci U S A. 2002;99:12386–90. doi:10.1073/pnas.192360099.

    Article  PubMed  CAS  Google Scholar 

  12. Schulman HMPPWA, Gauthier Y, Shyamala G. Transferrin receptor and ferritin levels during murine mammary gland development. Biochim Biophys Acta. 1989;1010:1–6. doi:10.1016/0167-4889(89)90176-6.

    Article  PubMed  CAS  Google Scholar 

  13. Futran J, Kemp JD, Field EH, Vora A, Ashman RF. Transferrin receptor synthesis is an early event in B cell activation. J Immunol. 1989;143:787–92.

    PubMed  CAS  Google Scholar 

  14. Brekelmans P, van Soest P, Voerman J, Platenburg PP, Leenen PJ, van Ewijk W. Transferrin receptor expression as a marker of immature cycling thymocytes in the mouse. Cell Immunol. 1994;159:331–9. doi:10.1006/cimm.1994.1319.

    Article  PubMed  CAS  Google Scholar 

  15. Ross SR. MMTV and the immune system. Adv Pharm. 1997;39:21–46.

    Article  CAS  Google Scholar 

  16. Rassa JC, Meyers JL, Zhang Y, Kudaravalli R, Ross SR. Murine retroviruses activate B cells via interaction with Toll-like receptor 4. Proc Natl Acad Sci U S A. 2002;99:2281–6. doi:10.1073/pnas.042355399.

    Article  PubMed  CAS  Google Scholar 

  17. Burzyn D, Rassa JC, Kim D, Nepomnaschy I, Ross SR, Piazzon I. Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. J Virol. 2004;78:576–84. doi:10.1128/JVI.78.2.576-584.2004.

    Article  PubMed  CAS  Google Scholar 

  18. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783–801. doi:10.1016/j.cell.2006.02.015.

    Article  PubMed  CAS  Google Scholar 

  19. Mertz JA, Simper MS, Lozano MM, Payne SM, Dudley JP. Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a complex retrovirus. J Virol. 2005;79:14737–47. doi:10.1128/JVI.79.23.14737-14747.2005.

    Article  PubMed  CAS  Google Scholar 

  20. Indik S, Gunzburg WH, Salmons B, Rouault F. A novel, mouse mammary tumor virus encoded protein with Rev-like properties. Virol. 2005;337:1–6. doi:10.1016/j.virol.2005.03.040.

    Article  CAS  Google Scholar 

  21. Salmons B, Erfle V, Brem G, Günzburg WH. Naf, a trans-regulating negative-acting factor within the mouse mammary tumor virus open reading frame region. J Virol. 1990;64:6355–9.

    PubMed  CAS  Google Scholar 

  22. Rouault F, Nejad Asl SB, Rungaldier S, Fuchs E, Salmons B, Gunzburg WH. Promoter complex in the central part of the mouse mammary tumor virus long terminal repeat. J Virol. 2007;81:12572–81. doi:10.1128/JVI.00351-07.

    Article  PubMed  CAS  Google Scholar 

  23. Michalides R, van Nie R, Nusse R, Hynes NE, Groner B. Mammary tumor virus induction loci in GR and DBAf mice contain one provirus of the mouse mammary tumor virus. Cell 1981;23:165–73. doi:10.1016/0092-674(81)90281-6.

    Article  PubMed  CAS  Google Scholar 

  24. Morris VL, Medeiros E, Ringold GM, Bishop JM, Varmus HE. Comparison of mouse mammary tumor virus-specific DNA in inbred, wild and Asian mice, and in tumors and normal organs from inbred mice. J Mol Biol. 1977;114:73–91. doi:10.1016/0022-836(77)90284-4.

    Article  PubMed  CAS  Google Scholar 

  25. Baillie GJ, van de Lagemaat LN, Baust C, Mager DL. Multiple groups of endogenous betaretroviruses in mice, rats and other mammals. J Virol. 2004;78:5784–98. doi:10.1128/JVI.78.11.5784-5798.2004.

    Article  PubMed  CAS  Google Scholar 

  26. Martin P, Ruiz SR, Martinez del Hoyo G, Anjuere F, Vargas HH, Lopez-Bravo M, et al. Dramatic increase in lymph node dendritic cell numbers during infection by the mouse mammary tumor virus occurs by a CD62L-dependent blood-borne DC recruitment. Blood 2002;99:1282–8. doi:10.1182/blood.V99.4.1282.

    Article  PubMed  CAS  Google Scholar 

  27. Vacheron S, Luther SJ, Acha-Orbea H. Preferential infection of immature dendritic cells and B cells by mouse mammary tumor virus. J Immunol. 2002;168:3470–6.

    PubMed  CAS  Google Scholar 

  28. Courreges MC, Burzyn D, Nepomnaschy I, Piazzon I, Ross SR. Critical role of dendritic cells in mouse mammary tumor virus in vivo infection. J Virol. 2007;81:3769–77. doi:10.1128/JVI.02728-06.

    Article  PubMed  CAS  Google Scholar 

  29. O’Neill LAJ. The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2000;2000(44):1–11.

    Google Scholar 

  30. Jude BA, Pobezinskaya Y, Bishop J, Parke S, Medzhitov RM, Chervonsky AV, et al. Subversion of the innate immune system by a retrovirus. Nat Immunol. 2003;4:573–8. doi:10.1038/ni926.

    Article  PubMed  CAS  Google Scholar 

  31. Held W, Waanders G, Shakhov AN, Scarpellino L, Acha-Orbea H, MacDonald HR. Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission. Cell 1993;74:529–40. doi:10.1016/0092-8674(93)80054-I.

    Article  PubMed  CAS  Google Scholar 

  32. Ignatowicz L, Kappler J, Marrack P. The effects of chronic infection with a superantigen-producing virus. J Exp Med. 1992;175:917–23. doi:10.1084/jem.175.4.917.

    Article  PubMed  CAS  Google Scholar 

  33. Golovkina TV, Dudley JP, Ross SR. Superantigen activity is need for mouse mammary tumor virus spread within the mammary gland. J Immunol. 1998;161:2375–82.

    PubMed  CAS  Google Scholar 

  34. Finke D, Acha-Orbea H. Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs. Eur J Immunol. 2001;31:2603–11. doi:10.1002/1521-4141(200109)31:9<2603::AID-IMMU2603>3.0.CO;2-8.

    Article  PubMed  CAS  Google Scholar 

  35. Callahan R, Smith GH. MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways. Oncogene 2000;19:992–1001. doi:10.1038/sj.onc.1203276.

    Article  PubMed  CAS  Google Scholar 

  36. Faschinger A, Rouault F, Sollner J, Lukas A, Salmons B, Gunzburg WH, et al. Mouse mammary tumor virus integration site selection in human and mouse genomes. J Virol. 2008;82:13601–7.

    Article  CAS  Google Scholar 

  37. Golovkina TV, Prescott JA, Ross SR. Mouse mammary tumor virus-induced tumorigenesis in sag transgenic mice: a laboratory model of natural selection. J Virol. 1993;67:7690–4.

    PubMed  CAS  Google Scholar 

  38. Katz E, Lareef MH, Rassa JC, Grande SM, King LB, Russo J, et al. MMTV Env encodes an ITAM responsible for transformation of mammary epithelial cells in three-dimensional culture. J Exp Med. 2005;201:431–9. doi:10.1084/jem.20041471.

    Article  PubMed  CAS  Google Scholar 

  39. Ross SR, Schmidt JW, Katz E, Cappelli L, Hultine S, Gimmotty P, et al. An immunoreceptor tyrosine activation motif in the Mouse Mammary Tumor Virus envelope protein plays a role in virus-induced mammary tumors. J Virol. 2006;80:9000–8. doi:10.1128/JVI.00788-06.

    Article  PubMed  CAS  Google Scholar 

  40. Lu J, Lin WH, Chen SY, Longnecker R, Tsai SC, Chen CL, et al. Syk tyrosine kinase mediates Epstein–Barr Virus latent membrane protein 2A-induced cell migration in epithelial cells. J Biol Chem. 2006;281:8806–14. doi:10.1074/jbc.M507305200.

    Article  PubMed  CAS  Google Scholar 

  41. Morrison JA, Raab-Traub N. Roles of the ITAM and PY motifs of Epstein–Barr Virus latent membrane protein 2A in the inhibition of epithelial cell differentiation and activation of β-catenin signaling. J Virol. 2005;79:2375–82. doi:10.1128/JVI.79.4.2375-2382.2005.

    Article  PubMed  CAS  Google Scholar 

  42. Lee H, Guo J, Li M, Choi JK, DeMaria M, Rosenzweig M, et al. Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi’s sarcoma-associated herpesvirus. Mol Cell Biol. 1998;18:5219–28.

    PubMed  CAS  Google Scholar 

  43. Maeda N, Palmarini M, Murgia C, Fan H. Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA. Proc Natl Acad Sci U S A. 2001;98:4449–54. doi:10.1073/pnas.071547598.

    Article  PubMed  CAS  Google Scholar 

  44. Rai SK, Duh FM, Vigdorovich V, Danilkovitch-Miagkova A, Lerman MI, Miller AD. Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci U S A. 2001;98:4443–8. doi:10.1073/pnas.071572898.

    Article  PubMed  CAS  Google Scholar 

  45. Wootton SK, Halbert CL, Miller AD. Sheep retrovirus structural protein induces lung tumours. Nature 2005;434:904–7. doi:10.1038/nature03492.

    Article  PubMed  CAS  Google Scholar 

  46. Michalides R, Wagenaar E, Hilkens J, Hilgers J, Groner B, Hynes NE. Acquisition of proviral DNA of mouse mammary tumor virus in thymic leukemia cells from GR mice. J Virol. 1982;43:819–29.

    PubMed  CAS  Google Scholar 

  47. Yanagawa SI, Kakimi K, Tanaka H, Murakami A, Nakagawa Y, Kubo Y, et al. Mouse mammary tumor virus with rearranged long terminal repeats causes murine lymphomas. J Virol. 1993;67:112–8.

    PubMed  CAS  Google Scholar 

  48. Bhadra S, Lozano MM, Dudley JP. Conversion of mouse mammary tumor virus to a lymphomagenic virus. J Virol. 2005;79:12592–6. doi:10.1128/JVI.79.19.12592-12596.2005.

    Article  PubMed  CAS  Google Scholar 

  49. Yanagawa S, Lee JS, Kakimi K, Matsuda Y, Honjo T, Ishimoto A. Identification of Notch1 as a frequent target for provirus insertional mutagenesis in T-cell lymphomas induced by leukemogenic mutants of mouse mammary tumor virus. J Virol. 2000;74:9786–91. doi:10.1128/JVI.74.20.9786-9791.2000.

    Article  PubMed  CAS  Google Scholar 

  50. Broussard DR, Mertz JA, Lozano M, Dudley JP. Selection for c-myc integration sites in polyclonal T-cell lymphomas. J Virol. 2002;76:2087–99. doi:10.1128/jvi.76.5.2087-2099.2002.

    Article  PubMed  CAS  Google Scholar 

  51. Bentvelzen P, Brinkhof J, Haaijman JJ. Genetic control of endogenous murine mammary tumour viruses reinvestigated. Eur J Cancer 1978;14:1137–47. doi:10.1016/0014-2964(78)90070-1.

    PubMed  CAS  Google Scholar 

  52. Outzen HC, Morrow D, Shultz LD. Attenuation of exogenous murine mammary tumor virus virulence in the C3H/HeJ mouse substrain bearing the Lps mutation. J Natl Cancer Inst. 1985;75:917–23.

    PubMed  CAS  Google Scholar 

  53. Held W, Waanders GA, MacDonald HR, Acha-Orbea H. MHC class II hierarchy of superantigen presentation predicts efficiency of infection with mouse mammary tumor virus. Int Immunol. 1994;6:1403–7. doi:10.1093/intimm/6.9.1403.

    Article  PubMed  CAS  Google Scholar 

  54. Pucillo C, Cepeda R, Hodes RJ. Expression of a MHC Class II transgene determines superantigenicity and susceptibility to mouse mammary tumor virus infection. J Exp Med. 1993;178:1441–5. doi:10.1084/jem.178.4.1441.

    Article  PubMed  CAS  Google Scholar 

  55. Beutner U, Draus E, Kitamura D, Rajewsky K, Huber BT. B cells are essential for murine mammary tumor virus transmission, but not for presentation of endogenous superantigens. J Exp Med. 1994;179:1457–66. doi:10.1084/jem.179.5.1457.

    Article  PubMed  CAS  Google Scholar 

  56. Pobezinskaya Y, Chervonsky AV, Golovkina TV. Initial stages of mammary tumor virus infection are superantigen independent. J Immunol. 2004;172:5582–7.

    PubMed  CAS  Google Scholar 

  57. Purdy A, Case L, Duvall M, Overstrom-Coleman M, Monnier N, Chervonsky A, et al. Unique resistance of I/LnJ mice to a retrovirus is due to sustained IFN-gamma dependent production of virus-neutralizing antibodies. J Exp Med. 2003;197:233–43. doi:10.1084/jem.20021499.

    Article  PubMed  CAS  Google Scholar 

  58. Okeoma CM, Shen M, Ross SR. A novel block to mouse mammary tumor virus infection of lymphocytes in B10.BR mice. J Virol. 2008;82:1314–22. doi:10.1128/JVI.01848-07.

    Article  PubMed  CAS  Google Scholar 

  59. MacDearmid CC, Case LK, Starling CL, Golovkina TV. Gradual elimination of retroviruses in YBR/Ei mice. J Virol. 2006;80:2206–15. doi:10.1128/JVI.80.5.2206-2215.2006.

    Article  PubMed  CAS  Google Scholar 

  60. Bhadra S, Lozano MM, Payne SM, Dudley JP. Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens. PLoS Pathog. 2006;2w:e128. doi:10.1371/journal.ppat.0020128.

    Article  CAS  Google Scholar 

  61. Czarneski J, Meyers J, Peng T, Abraham V, Ross SR. Interleukin-4 up-regulates mouse mammary tumor virus expression but is not required for in vivo virus spread. J Virol. 2001;75:11886–90. doi:10.1128/JVI.75.23.11886-11890.2001.

    Article  PubMed  CAS  Google Scholar 

  62. Day NK, Witkin SS, Sarkar NH, Kinne D, Jussawalla DJ, Levin A, et al. Antibodies reactive with murine mammary tumor virus in sera of patients with breast cancer: geographic and family studies. Proc Natl Acad Sci U S A. 1981;78:2483–7. doi:10.1073/pnas.78.4.2483.

    Article  PubMed  CAS  Google Scholar 

  63. Mesa-Tejada R, Oster MW, Fenoglio CM, Magidson J, Spiegelman S. Diagnosis of primary breast carcinoma through immunohistochemical detection of antigen related to mouse mammary tumor virus in metastatic lesions: a report of two cases. Cancer 1982;49:261–8. doi:10.002/1097-0142(19820115)49:2<261::AID-CNCR2820490211>3.0.CO;2-3.

    Article  PubMed  CAS  Google Scholar 

  64. Goedert JJ, Rabkin CS, Ross SR. Prevalence of serologic reactivity against four strains of mouse mammary tumor virus among U.S. women with breast cancer. Br J Cancer 2006;94:548–51. doi:10.1038/sj.bjc.6602977.

    Article  PubMed  CAS  Google Scholar 

  65. Pogo BGT, Melana SM, Holland JF, Mandeli JF, Polotti S, Casalini P, et al. Sequences homologous to the mouse mammary tumor virus env gene in human breast cancer correlate with overexpression of laminin receptor. Clin Cancer Res. 1999;5:2108–11.

    PubMed  CAS  Google Scholar 

  66. Wang Y, Holland JF, Bleiweiss IJ, Melana S, Liu X, Pelisson I, et al. Detection of mammary tumor virus ENV gene-like sequences in human breast cancer. Cancer Res. 1995;35:5173–9.

    Google Scholar 

  67. Etkind P, Du J, Khan A, Pillitteri J, Wiernik PH. Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient. Clin Cancer Res. 2000;6:1273–8.

    PubMed  CAS  Google Scholar 

  68. Liu B, Wang Y, Melana SM, Pelisson I, Najfeld V, Holland JF, et al. Identification of a proviral structure in human breast cancer. Cancer Res. 2001;61:1754–9.

    PubMed  CAS  Google Scholar 

  69. Mant C, Hodgson S, Hobday R, D’Arrigo C, Cason J. A viral aetiology for breast cancer: time to re-examine the postulate. Intervirol. 2003;47:2–13. doi:10.1159/000076636.

    Article  Google Scholar 

  70. Witt A, Hartmann B, Marton E, Zeillinger R, Schreiber M, Kubista E. The mouse mammary tumor virus-like env gene sequence is not detectable in breast cancer tissue of Austrian patients. Oncol Rep. 2003;10:1025–9.

    PubMed  CAS  Google Scholar 

  71. Bindra A, Muradrasoli S, Kisekka R, Nordgren H, Warnberg F, Blomberg J. Search for DNA of exogenous mouse mammary tumor virus-related virus in human breast cancer samples. J Gen Virol. 2007;88:1806–9. doi:10.1099/vir.0.82767-0.

    Article  PubMed  CAS  Google Scholar 

  72. Lasfargues EY, Coutinho WG, Dion AS. A human breast tumor cell line (BT474) that supports mammary tumor virus replication. In Vitro 1979;15:723–8. doi:10.1007/BF02618252.

    Article  PubMed  CAS  Google Scholar 

  73. Howard DK, Schlom J. Isolation of a series of novel variants of murine mammary tumor viruses with broadened host range. Int J Cancer 1980;25:647–54. doi:10.1002/ijc.2910250515.

    Article  PubMed  CAS  Google Scholar 

  74. Wang E, Albritton L, Ross SR. Identification of the segments of the mouse transferrin receptor 1 required for mouse mammary tumor virus infection. J Biol Chem. 2006;281:10243–9. doi:10.1074/jbc.M511572200.

    Article  PubMed  CAS  Google Scholar 

  75. Zhang Y, Rassa JC, deObaldia EM, Albritton L, Ross SR. Identification of the mouse mammary tumor virus envelope receptor-binding domain. J Virol. 2003;77:10468–78. doi:10.1128/JVI.77.19.10468-10478.2003.

    Article  PubMed  CAS  Google Scholar 

  76. Indik S, Gunzburg WH, Salmons B, Rouault F. Mouse mammary tumor virus infects human cells. Cancer Res. 2005;65:6651–9. doi:10.1158/0008-5472.CAN-04-2609.

    Article  PubMed  CAS  Google Scholar 

  77. Indik S, Gunzburg WH, Kulich P, Salmons B, Rouault F. Rapid spread of mouse mammary tumor virus in cultured human breast cells. Retrovirol. 2007;4:73. doi:10.1186/1742-4690-4-73.

    Article  CAS  Google Scholar 

  78. Titus-Ernstoff L, Egan KM, Newcomb PA, Baron JA, Stampfer M, Greenberg ER, et al. Exposure to breast milk in infancy and adult breast cancer risk. J Natl Cancer Inst. 1998;12:921–4. doi:10.1093/jnci/90.12.921.

    Article  Google Scholar 

  79. Kampert JB, Whittemore AS, Paffenbarger RS Jr. Combined effect of childbearing, menstrual events, and body size on age-specific breast cancer risk. Am J Epidemiol. 1988;128:962–79.

    PubMed  CAS  Google Scholar 

  80. MacMahon B, Cole P, Brown J. Etiology of human breast cancer: a review. Natl Canc Inst. 1973;50:21–42.

    CAS  Google Scholar 

  81. Stewart THM, Sage RD, Stewart AFR, Cameron DW. Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus. Br J Cancer 2000;82:446–51. doi:10.1054/bjoc.1999.0941.

    Article  PubMed  CAS  Google Scholar 

  82. Luther SA, Maillard I, Luthi F, Scarpellino L, Diggelmann H, Acha-Orbea H. Early neutralizing antibody response against mouse mammary tumor virus; critical role of viral infection and superantigen-reactive T cells. J Immunol. 1997;159:2807–14.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology/Abramson Family Cancer Center, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA, 1914, USA

    Susan R. Ross

Authors
  1. Susan R. Ross
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Susan R. Ross.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ross, S.R. MMTV Infectious Cycle and the Contribution of Virus-encoded Proteins to Transformation of Mammary Tissue. J Mammary Gland Biol Neoplasia 13, 299–307 (2008). https://doi.org/10.1007/s10911-008-9090-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-008-9090-8

Keywords