Abstract 821: Human mammary tumor virus(HMTV) is deeply involved in breast cancer and metastasis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.821-821
• Main Authors: Holland, James F., Melana, Stella, Jaffer, Shabnam, Etkind, Polly, Nartey, Teiko, Lee, Tina, Pogo, Beatriz G.T.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-821

Human Mammary Tumor Virus (HMTV), a betaretrovirus 90-95% homologous to Mouse Mammary Tumor Virus (MMTV), present in 40% of American women's breast cancers, but not in the normal tissue from the same breast indicates an infection (Cancer Res 1995, 55:5173-79). Absence of murine intracisternal particles and murine cyclo-oxygenase 2 by PCR and nanoString excludes contemporaneous mouse DNA, and thus MMTV contamination (Proc AACR 2014 #1595). We have detected the entire 9.9 kb proviral sequence. Proviral DNA is visible in nuclei by FISH, and budding virus was observed by EM. HMTV in cells is present in the milk of 8% of unselected American women, but in 21% if they had had a prior biopsy based upon clinical or radiologic suspicion of a mass. (Infectious Agents and Cancer 2014, 9:20). HMTV has been found in cells of 30 of 32 (94%) metastatic breast cancer effusions (MSSM cells). HMTV protein and virion RNA were detected in MSSM cells but not in normal human mammary epithelium. (J Virol Methods 2010,163:157-61). HMTV isolated from MSSM cells is infectious for B and T lymphocytes, MCF10A andF and human mammary epithelial cells (HMEC). Infection led to proviral insertion sites with different flanking sequences. Epithelial-mesenchymal transition was observed with upregulation of vimentin and downregulation of E-cadherin. Restriction factors including the cytidine deaminase APOBEC G and F, TRIM 5, 21 and 25 and Tetherin were also increased after in vitro HMTV infection. Epidemiologically, breast cancer is less frequent in 5 countries of Central and East and Asia (28-43/100,000/y. World Cancer Report 2014) where HMTV positivity in breast cancers ranges from 0 to 20%, compared to 7 countries of Western Europe and its former colonies in North and South America and Australia (47-92/100,000/y op.cit.) where 30 to 60% are positive. This correlates with indigenous mouse species, Mus musclus and M.castaneus in the East, and M. domesticus with much more HMTV in its genome in the West. HMTV positive lymphomas have been reported in patients with HMTV positive breast cancers (Clin Cancer Res 2004 10:56565-64). The parallel with MMTV behavior in the mouse with respect to breast cancer and lymphomas is striking. These composite data support a significant role of HMTV in human breast cancer and its metastatic process. Citation Format: James F. Holland, Stella Melana, Shabnam Jaffer, Polly Etkind, Teiko Nartey, Tina Lee, Beatriz G.T. Pogo. Human mammary tumor virus(HMTV) is deeply