- ASSISTANT PROFESSOR Medicine, Hematology and Medical Oncology
M.Sci, University of Buenos Aires
Ph.D, University of Buenos Aires
Post-doctoral, Mount Sinai School of Medicine
We detected DNA sequences of a retrovirus called Human Mammary Tumor Virus (HMTV), which is 90-98% homologous to Mouse Mammary Tumor Virus (the etiological agent of mammary tumors in mice), in 38% of breast cancer specimens of 594 American women studied. These sequences did not have significant homology to any human gene or endogenous retrovirus (HERV).
In addition, HMTV viral particles with betaretroviral characteristics have been isolated from metastatic breast cancer cells. Expression of HMTV proteins has been observed by western blot, fluorescence-activated cell sorting analysis and immunofluorescence assays in metastatic breast cancer cells but not in normal mammary epithelial cells.
Recently, it was shown that HMTV isolated from metastatic breast cancer cells is able to infect primary cultures of human mammary epithelial cells, peripheral blood mononuclear cells, dendritic cells of healthy donors and the following cell lines: MCF10A, MCF10F, 293T cells,Jurkat and Ramos cells.
Epithelial Mesenchymal transition is observed when healthy breast epithelial cells become neoplastic cells. In HMTV infected MCF10F cells, expression of proteins characteristic of epithelial cells decreases and the expression of proteins characteristic of mesenchymal cells increased. These changes are similar to those occurring during the EMT process in breast malignancy.
The focus of our investigation is the role of this retrovirus in human pathogenesis.
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 research 1995 Nov; 55(22).
Pogo BG, Melana SM, Holland JF, Mandeli JF, Pilotti S, Casalini P, Ménard S. Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor. Clinical cancer research : an official journal of the American Association for Cancer Research 1999 Aug; 5(8).
Melana SM, Holland JF, Pogo BG. Search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals. Clinical cancer research : an official journal of the American Association for Cancer Research 2001 Feb; 3(2).
Liu B, Wang Y, Melana SM, Pelisson I, Najfeld V, Holland JF, Pogo BG. Identification of a proviral structure in human breast cancer. Cancer research 2001 Feb; 61(4).
Melana SM, Nepomnaschy I, Sakalian M, Abbott A, Hasa J, Holland JF, Pogo BG. Characterization of viral particles isolated from primary cultures of human breast cancer cells. Cancer research 2007 Sep; 67(18).
Melana SM, Nepomnaschy I, Hasa J, Djougarian A, Djougarian A, Holland JF, Pogo BG. Detection of human mammary tumor virus proteins in human breast cancer cells. Journal of virological methods 2010 Jan; 163(1).
Waddell N, Stein SR, Wagner SA, Bennett I, Djougarian A, Melana S, Jaffer S, Holland JF, Pogo BG, Gonda TJ, Brown MA, Leo P, Saunders NA, McMillan NA, Cocciardi S, Vargas AC, Lakhani SR, Chenevix-Trench G, Newman B, Francis GD. Morphological and molecular analysis of a breast cancer cluster at the ABC Studio in Toowong. Pathology 2012 Aug; 44(5).
Nartey T, Moran H, Marin T, Arcaro KF, Anderton DL, Etkind P, Holland JF, Melana SM, Pogo BG. Human Mammary Tumor Virus (HMTV) sequences in human milk. Infectious agents and cancer 2014; 9.
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Dr. Melana did not report having any of the following types of financial relationships with industry during 2014 and/or 2015: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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