Tumor Biology

, Volume 35, Issue 8, pp 8077–8086 | Cite as

Detection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patients

  • Wasifa Naushad
  • Talha bin Rahat
  • Miriam Kathleen Gomez
  • Muhammad Taimoor Ashiq
  • Muhammad Younas
  • Hajra Sadia
Research Article


Mouse mammary tumor virus (MMTV) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. The hypothesis that a retrovirus homologous to MMTV is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. Therefore, the detection of MMTV-like exogenous sequences in 30–40 % of invasive breast cancer has increased attention towards this hypothesis. To detect the prevalence of MMTV in Pakistani population, 666-bp-long MMTV envelop and 630-bp LTR sequences were amplified from breast cancer patient samples (tissue biopsies and peripheral blood) using mouse with mammary tumor as control. MMTV-like virus env and LTR DNA sequences were detected in 20 and 26 % of breast tumor samples, respectively, from the total of 80 breast cancer patients’ blood and tissue samples. No significant association was observed between age, grade of disease, and lymph node involvement with the prevalence of MMTV-like sequences. Our data add to the growing number of studies implicating MMTV-like virus in human breast cancer, but still clear causal association of MMTV to breast cancer remains to be reputable.


Mouse mammary tumor virus Breast cancer MMTV envelop gene MMTV LTR gene 


  1. 1.
    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(Pt 6):1806–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Callahan R. MMTV-induced mutations in mouse mammary tumors: their potential relevance to human breast cancer. Breast Cancer Res Treat. 1996;39(1):33–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Chan PKS, Chan DPC, To KF, Yu MY, Cheung JLK, Cheng AF. Evaluation of extraction methods from paraffin wax embedded tissues for PCR amplification of human and viral DNA. J Clin Pathol. 2001;54(5):401–3.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Coffin JM, Hughes SH, Varmus HE. Retroviruses. Cold Spring Harbor: Cold Spring Harbor Laboratory; 1997.Google Scholar
  5. 5.
    Daniel RL, Daniel Z, Bin W, Jeffrey AC, Robert HS. Real-time observation of transcription initiation and elongation on an endogenous yeast gene. Science. 2011;332:475–8. doi: 10.1126/science.1202142.
  6. 6.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    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(4):1273–8.PubMedGoogle Scholar
  8. 8.
    Etkind P, Stewart A, Wiernik PH. Mouse mammary tumor virus (MMTV)-like DNA sequences in the breast tumors of father, mother, and daughter. Infectious Agents and Cancer 2008. 2008;3:2. doi: 10.1186/1750-9378-3-2.CrossRefGoogle Scholar
  9. 9.
    Feldman SP, Schlom J, Spiegelman S. Further evidence for oncornaviruses in human milk: the production of cores. Proc Natl Acad Sci U S A. 1973;70:1976–80.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Ford CE, Faedo M, Crouch R, Lawson JS, Rawlinson WD. Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women. Cancer Res. 2004;64(14):4755–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Hachana M, Trimeche M, Ziadi S, Amara K, Gaddas N, Mokni M, et al. Prevalence and characteristics of the MMTV-like associated breast carcinomas in Tunisia. Cancer Lett. 2008;271(2):222–30.PubMedCrossRefGoogle Scholar
  12. 12.
    Hohenadl C, Gunzburg WH, Salmons B, Indik S. The 5′ leader sequence of mouse mammary tumor virus enhances expression of the envelope and reporter genes. J Gen Virol. 2012;93(Pt 2):308–18. doi: 10.1099/vir.0.035196-0.PubMedCrossRefGoogle Scholar
  13. 13.
    Holder Jr WD, Wells Jr SA. Antibody reacting with the murine mammary tumor virus in the serum of patients with breast carcinoma: a possible serological detection method for breast carcinoma. Cancer Res. 1983;43:239–44.PubMedGoogle Scholar
  14. 14.
    Lawson JS, Gunzburg WH, Whitaker NJ. Viruses and human breast cancer. Future Microbiol. 2006;1(1):33–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Lawson JS, Glenn WK, Salmons B, Ye Y, Heng B, Moody P, et al. Mouse mammary tumor virus-like sequences in human breast cancer. Cancer Res. 2010. doi: 10.1158/0008-5472.PubMedGoogle Scholar
  16. 16.
    Levine PH, Pogo BG, Klouj A, Coronel S, Woodson K, Melana SM, et al. Increasing evidence for a human breast carcinoma virus with geographic differences. Cancer. 2004;101(4):721–6.PubMedCrossRefGoogle Scholar
  17. 17.
    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(4):1754–9.PubMedGoogle Scholar
  18. 18.
    Luo T, Wu XT, Zhang MM, Qian K. Study of mouse mammary tumor virus-like gene sequences expressing in breast tumors of Chinese women. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006;37(6):844–6. 851.PubMedGoogle Scholar
  19. 19.
    Melana SM, Holland JF, Pogo BG. Search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals. Clin Cancer Res. 2001;7(2):283–4.PubMedGoogle Scholar
  20. 20.
    Mesa-Tejada R, Keydar I, Ramanarayanan M, Ohno T, Fenoglio C, Spiegelman S. Detection in human breast carcinomas of an antigen immunologically related to a group-specific antigen of mouse mammary tumor virus. Proc Natl Acad Sci U S A. 1978;75:1529–33.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Michalides R, Spiegelman S, Schlom J. Biochemical characterization of putative subviral particulates from human malignant breast tumors. Cancer Res. 1975;35:1003–8.PubMedGoogle Scholar
  22. 22.
    Moore PS, Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer. 2010;10(12):878–89. doi: 10.1038/nrc2961.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Ohno T, Mesa-Tejada R, Keydar I, Ramanarayanan M, Bausch J, Spiegelman S. Human breast carcinoma antigen is immunologically related to the polypeptide of the group-specific glycoprotein of mouse mammary tumor virus. Proc Natl Acad Sci U S A. 1979;76:2460–4.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Pogo BG, Melana SM, Holland JF, Mandeli JF, Pilotti S, Casalini P, et al. Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor. Clin Cancer Res. 1999;5(8):2108–11.PubMedGoogle Scholar
  25. 25.
    Pogo BG, Holland JF, Levine PH. Human mammary tumor virus in inflammatory breast cancer. Cancer. 2010;116(11):2741–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Salmons B, Gunzburg WH. Current perspectives in the biology of mouse mammary tumour virus. Virus Res. 1987;8(2):81–102.PubMedCrossRefGoogle Scholar
  27. 27.
    Spiegelman S, Axel R, Schlom J. Virus-related RNA in human and mouse mammary tumors. J Natl Cancer Inst. 1972;48:1205–11.PubMedGoogle Scholar
  28. 28.
    Stewart TH, Sage RD, Stewart AF, Cameron DW. Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus. Br J Cancer. 2000;82(2):446–51.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Sohail S, Alam SN. Breast cancer in Pakistan: awareness and early detection. J Coll Phys Surg Pak. 2007;17:711–2.Google Scholar
  30. 30.
    Wang Y, Jiang JD, Xu D, Li Y, Qu C, Holland JF, et al. A mouse mammary tumor virus-like long terminal repeat superantigen in human breast cancer. Cancer Res. 2004;64(12):4105–11.PubMedCrossRefGoogle Scholar
  31. 31.
    Wang Y, Pelisson I, Melana SM, Go V, Holland JF, Pogo BG. MMTV-like env gene sequences in human breast cancer. Arch Virol. 2001;146(1):171–80.PubMedCrossRefGoogle Scholar
  32. 32.
    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;55:5173–9.PubMedGoogle Scholar
  33. 33.
    Witkin SS, Sarkar NH, Kinne DW, Breed CN, Good RA, Day NK. Antigens and antibodies cross-reactive to the murine mammary tumor virus in human breast cyst fluids. J Clin Invest. 1981;67:216–22.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    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(4):1025–9.PubMedGoogle Scholar
  35. 35.
    Zangen R, Harden S, Cohen D, Parrella P, Sidransky D. Mouse mammary tumor-like env gene as a molecular marker for breast cancer? Int J Cancer. 2002;102(3):304–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Zapata-Benavides P, Saavedra-Alonso S, Zamora-Avila D, Vargas-Rodarte C, Barrera-Rodriguez R, Salinas-Silva J, et al. Mouse mammary tumor virus-like gene sequences in breast cancer samples of Mexican women. Intervirology. 2007;50(6):402–7.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Wasifa Naushad
    • 1
  • Talha bin Rahat
    • 1
  • Miriam Kathleen Gomez
    • 1
  • Muhammad Taimoor Ashiq
    • 1
  • Muhammad Younas
    • 2
  • Hajra Sadia
    • 1
  1. 1.Atta-Ur-Rahman School of Applied Biosciences (ASAB)National University of Sciences and Technology (NUST)IslamabadPakistan
  2. 2.Benazir Bhutto HospitalRawalpindiPakistan

Personalised recommendations