Case Study Of Hmtv

Breast cancer risk appears to be derived from a combination of factors, including genetic susceptibility, exposure to carcinogens, diet and other lifestyle factors, and harmful mutations that accumulate with age. However, the fact that some very young women with no obvious exposures to breast carcinogens or family history of breast cancer develop the disease suggests that at least one other important factor also influences risk. After considerable skepticism, debate and study, infection with certain viruses has emerged as a breast cancer risk factor. Now a new study has reported that a virus originally transmitted to humans from mice and mutated thereafter may be responsible for some cases of breast cancer, including some of the most aggressive.

Mouse mammary tumor virus

Mouse mammary tumor virus (MMTV) promotes the development of mammary tumors in mice without additional exposure to any carcinogens. In fact, generations of mice infected with the virus have been used in breast cancer studies since the virus reliably induces mammary tumors in carriers. Transmission of MMTV to offspring is automatic since it is passed on to mouse pups in the breast milk of their mothers and through daily physical contact. MMTV is also found in wild mice (i.e., living freely, not bred in the laboratory).

DNA with approximately 95% of MMTV sequences has been found in some human breast cancers. The worldwide incidence of breast cancer appears to correspond to the ranges of different species of wild mice, with the highest rate found in countries where Mus domesticus is the predominant species of house mouse. This has led some researchers to conclude that humans have acquired MMTV from mice; the human strain of this virus has been named human mammary tumor virus (HMTV).

Latest research links HMTV to breast cancer

The study referenced at the beginning of this new article makes the case that HMTV can be a cause of breast cancer. HMTV has been found in approximately 40% of U.S. women's breast cancers, including in studies using techniques to rule out mouse DNA contamination. Asian countries have lower rates of breast cancer (29 to 43 per 100,000 per year) than Western European countries and their former colonies (47 to 92 per 100,000 per year), a difference that could be explained in part by a lower rate of HMTV-related breast cancer in Asia. The Mus castaneus and Mus musculus found in Asia have lower rates of MMTV than the Mus domesticus found in the West.

HMTV has been found in the breast milk of approximately 8% of the general U.S. female population and 21% of women biopsied for breast cancer. HMTV obtained from metastatic breast cells has been shown to be capable of infecting human breast epithelial cells in the laboratory. When non-cancerous human breast epithelial cells are infected with HMTV, they undergo molecular changes associated with epithelial-mesenchymal transition (EMT). EMT enables an epithelial cell to acquire enhanced migratory capacity and invasiveness, as well as increased resistance to apoptosis (programmed cell death). HMTV sequences are more prevalent in pregnancy-associated, familial and inflammatory breast cancer than in unselected non-familial samples, consistent with a link to more aggressive breast cancer types.

The authors have detected HMTV in 94% of primary cultures of metastatic breast cells obtained from effusion fluids, thereby establishing a direct connection between the presence of HMTV and metastatic breast cancer. In addition, HMTV found in primary breast tumors has also been found in their associated positive axillary lymph nodes. These results together suggest a link between HMTV and breast cancer aggressiveness. The authors conclude that the study of HMTV represents a new avenue of breast cancer research involving epidemiology, etiology, molecular mechanisms, diagnosis, prevention and treatment.

Tags:BCRiskPreventionNews, familialBreastCancer, familyHistoryNews, IBC, virus

Selected breast cancer studies

Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control StudyHuman mammary tumor virus(HMTV) is deeply involved in breast cancer and metastasisHuman Mammary Tumor Virus (HMTV) sequences in human milkDetection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patientsEpstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast CancerMouse mammary tumor like virus sequences in breast milk from healthy lactating womenHuman mammary tumor virus in inflammatory breast cancerProgression from Normal Breast Pathology to Breast Cancer Is Associated with Increasing Prevalence of Mouse Mammary Tumor Virus-Like Sequences in Men and WomenBreast cancer incidence highest in the range of one species of house mouse, Mus domesticus

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386. doi: 10.1002/ijc.29210.[PubMed][Cross Ref]

2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262.[PubMed][Cross Ref]

3. Hortobagyi GN, de la Garza SJ, Pritchard K, Amadori D, Haidinger R, Hudis CA, Khaled H, Liu MC, Martin M, Namer M, O’haughnessy JA, Shen ZZ, Albain KS, ABREAST I. The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer. 2005;6(5):391–401. doi: 10.3816/CBC.2005.n.043.[PubMed][Cross Ref]

4. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893–1907. doi: 10.1158/1055-9965.EPI-10-0437.[PubMed][Cross Ref]

5. Amarante MK, Watanabe MA. The possible involvement of virus in breast cancer. J Cancer Res Clin Oncol. 2009;135(3):329–337. doi: 10.1007/s00432-008-0511-2.[PubMed][Cross Ref]

6. Lawson JS. Do Viruses Cause Breast Cancer? In: Verma M, editor. Cancer Epidemiology. Totowa: Humana Press; 2009. pp. 421–438. [PubMed]

7. Callahan R, Smith GH. MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways. Oncogene. 2000;19(8):992–1001. doi: 10.1038/sj.onc.1203276.[PubMed][Cross Ref]

8. Callahan R, Smith GH. Common integration sites for MMTV in viral induced mouse mammary tumors. J Mammary Gland Biol Neoplasia. 2008;13(3):309–321. doi: 10.1007/s10911-008-9092-6.[PMC free article][PubMed][Cross Ref]

9. Wang Y, Holland JF, Bleiweiss IJ, Melana S, Liu X, Pelisson I, Cantarella A, Stellrecht K, Mani S, Pogo BG. Detection of mammary tumor virus env gene-like sequences in human breast cancer. Cancer Res. 1995;55(22):5173–5179.[PubMed]

10. Liu B, Wang Y, Melana SM, Pelisson I, Najfeld V, Holland JF, Pogo BG. Identification of a proviral structure in human breast cancer. Cancer Res. 2001;61(4):1754–1759.[PubMed]

11. Nartey T, Mazzanti CM, Melana S, Glenn WK, Bevilacqua G, Holland JF, Whitaker NJ, Lawson JS, Pogo BG. Mouse mammary tumor-like virus (MMTV) is present in human breast tissue before development of virally associated breast cancer. Infect Agent Cancer. 2017;12:1. doi: 10.1186/s13027-016-0113-6.[PMC free article][PubMed][Cross Ref]

12. Moore MA. Cancer control programs in East Asia: evidence from the international literature. J Prev Med Public Health. 2014;47(4):183–200. doi: 10.3961/jpmph.2014.47.4.183.[PMC free article][PubMed][Cross Ref]

13. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, editors. WHO Classification of Tumours of the Breast. Lyon: IARC; 2012.

14. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x.[PubMed][Cross Ref]

15. Ford CE, Tran D, Deng Y, Ta VT, Rawlinson WD, Lawson JS. Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women. Clin Cancer Res. 2003;9(3):1118–1120.[PubMed]

16. 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):4755–4759. doi: 10.1158/0008-5472.CAN-03-3804.[PubMed][Cross Ref]

17. Hachana M, Trimeche M, Ziadi S, Amara K, Gaddas N, Mokni M, Korbi S. Prevalence and characteristics of the MMTV-like associated breast carcinomas in Tunisia. Cancer Lett. 2008;271(2):222–230. doi: 10.1016/j.canlet.2008.06.001.[PubMed][Cross Ref]

18. Mazzanti CM, Al Hamad M, Fanelli G, Scatena C, Zammarchi F, Zavaglia K, Lessi F, Pistello M, Naccarato AG, Bevilacqua G. A mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma. Am J Pathol. 2011;179(4):2083–2090. doi: 10.1016/j.ajpath.2011.06.046.[PMC free article][PubMed][Cross Ref]

19. Cedro-Tanda A, Códova-Solis A, Juáez-Cedillo T, Pina-Jiméez E, Hernádez-Caballero ME, Moctezuma-Meza C, Castelazo-Rico G, Góez-Delgado A, Monsalvo-Reyes AC, Salamanca-Góez FA, Arenas-Aranda DJ, Garcí-Hernádez N. Prevalence of HMTV in breast carcinomas and unaffected tissue from Mexican women. BMC Cancer. 2014;14:942. doi: 10.1186/1471-2407-14-942.[PMC free article][PubMed][Cross Ref]

20. 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):1273–1278.[PubMed]

21. Glenn WK, Heng B, Delprado W, Iacopetta B, Whitaker NJ, Lawson JS. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer. PLoS One. 2012;7(11):e48788. doi: 10.1371/journal.pone.0048788.[PMC free article][PubMed][Cross Ref]

22. Levine PH, Pogo BG, Klouj A, Coronel S, Woodson K, Melana SM, Mourali N, Holland JF. Increasing evidence for a human breast carcinoma virus with geographic differences. Cancer. 2004;101(4):721–726. doi: 10.1002/cncr.20436.[PubMed][Cross Ref]

23. Melana SM, Picconi MA, Rossi C, Mural J, Alonio LV, Teyssie A, Holland JF, Pogo BG. [Detection of murine mammary tumor virus (MMTV) env gene-like sequences in breast cancer from Argentine patients] Medicina (B Aires) 2002;62(4):323–327.[PubMed]

24. Pogo BG, Melana SM, Holland JF, Mandeli JF, Pilotti S, Casalini P, Menard S. 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):2108–2111.[PubMed]

25. Slaoui M, El Mzibri M, Razine R, Qmichou Z, Attaleb M, Amrani M. Detection of MMTV-Like sequences in Moroccan breast cancer cases. Infect Agent Cancer. 2014;9:37. doi: 10.1186/1750-9378-9-37.[PMC free article][PubMed][Cross Ref]

26. 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):1806–1809. doi: 10.1099/vir.0.82767-0.[PubMed][Cross Ref]

27. Frank O, Verbeke C, Schwarz N, Mayer J, Fabarius A, Hehlmann R, Leib-Mosch C, Seifarth W. Variable transcriptional activity of endogenous retroviruses in human breast cancer. J Virol. 2008;82(4):1808–1818. doi: 10.1128/JVI.02115-07.[PMC free article][PubMed][Cross Ref]

28. Mant C, Gillett C, D’rrigo C, Cason J. Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies. Virology. 2004;318(1):393–404. doi: 10.1016/j.virol.2003.09.027.[PubMed][Cross Ref]

29. 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):1025–1029.[PubMed]

30. Fukuoka H, Moriuchi M, Yano H, Nagayasu T, Moriuchi H. No association of mouse mammary tumor virus-related retrovirus with Japanese cases of breast cancer. J Med Virol. 2008;80(8):1447–1451. doi: 10.1002/jmv.21247.[PubMed][Cross Ref]

31. Ahangar Oskouee M, Shahmahmoodi S, Jalilvand S, Mahmoodi M, Ziaee AA, Esmaeili HA, Mokhtari-Azad T, Yousefi M, Mollaei-Kandelous Y, Nategh R. No evidence of mammary tumor virus env gene-like sequences among Iranian women with breast cancer. Intervirology. 2014;57(6):353–356. doi: 10.1159/000366280.[PubMed][Cross Ref]

32. 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.[PubMed]

33. Naushad W, Bin Rahat T, Gomez MK, Ashiq MT, Younas M, Sadia H. Detection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patients. Tumour Biol. 2014;35(8):8077–8086. doi: 10.1007/s13277-014-1972-3.[PubMed][Cross Ref]

34. Reza MA, Reza MH, Mahdiyeh L, Mehdi F, Hamid ZN. Evaluation Frequency of Merkel Cell Polyoma, Epstein-Barr and Mouse Mammary Tumor Viruses in Patients with Breast Cancer in Kerman, Southeast of Iran. Asian Pac J Cancer Prev. 2015;16:7351–7357. doi: 10.7314/APJCP.2015.16.16.7351.[PubMed][Cross Ref]

35. Leong SP, Shen ZZ, Liu TJ, Agarwal G, Tajima T, Paik NS, Sandelin K, Derossis A, Cody H, Foulkes WD. Is breast cancer the same disease in Asian and Western countries. World J Surg. 2010;34(10):2308–2324. doi: 10.1007/s00268-010-0683-1.[PMC free article][PubMed][Cross Ref]

36. 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):446–451. doi: 10.1054/bjoc.1999.0941.[PMC free article][PubMed][Cross Ref]

37. Glenn WK, Salmons B, Lawson JS, Whitaker NJ. Mouse mammary tumor-like virus and human breast cancer. Breast Cancer Res Treat. 2010;123(3):907–909. doi: 10.1007/s10549-010-1021-x.[PubMed][Cross Ref]

38. Holland JF, Pogo BG. Comment on the review by Joshi and Buehring. Breast Cancer Res Treat. 2012;136(1):303–307. doi: 10.1007/s10549-012-2078-5.[PubMed][Cross Ref]

39. Faedo M, Ford CE, Mehta R, Blazek K, Rawlinson WD. Mouse mammary tumor-like virus is associated with p53 nuclear accumulation and progesterone receptor positivity but not estrogen positivity in human female breast cancer. Clin Cancer Res. 2004;10(13):4417–4419. doi: 10.1158/1078-0432.CCR-03-0232.[PubMed][Cross Ref]

40. Wang F, Hou J, Shen Q, Yue Y, Xie F, Wang X, Jin H. Mouse mammary tumor virus-like virus infection and the risk of human breast cancer. Am J Transl Res. 2014;6(3):248–266.[PMC free article][PubMed]

0 Replies to “Case Study Of Hmtv”

Lascia un Commento

L'indirizzo email non verrà pubblicato. I campi obbligatori sono contrassegnati *