Research Papers: Pathology:

Human saliva as route of inter-human infection for mouse mammary tumor virus

Chiara Maria Mazzanti, Francesca Lessi, Ivana Armogida, Katia Zavaglia, Sara Franceschi, Mohammad A.L. Hamad, Manuela Roncella, Matteo Ghilli, Antonio Boldrini, Giovanni Fanelli, Ivo Marchetti, Cristian Scatena, Jacob Hochman, Antonio Giuseppe Naccarato and Generoso Bevilacqua _

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Oncotarget. 2015; 6:18355-18363. https://doi.org/10.18632/oncotarget.4567

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Chiara Maria Mazzanti1,*, Francesca Lessi1,*, Ivana Armogida2,7, Katia Zavaglia2, Sara Franceschi1, Mohammad Al Hamad2,8, Manuela Roncella3, Matteo Ghilli3, Antonio Boldrini4, Paolo Aretini1, Giovanni Fanelli2, Ivo Marchetti2, Cristian Scatena2, Jacob Hochman5, Antonio Giuseppe Naccarato2,6, Generoso Bevilacqua1,2

1FPS – The Pisa Science Foundation, Pisa, Italy

2Department of Pathology, Pisa University Hospital, Pisa, Italy

3Breast Center, Department of Breast Surgery, Pisa University Hospital, Pisa, Italy

4Department of Neonatology, Pisa University Hospital, Pisa, Italy

5Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

6Laboratory of Pathology, “San Rossore” Hospital, Pisa, Italy

7Current address: Illumina Cambridge Ltd., Cambridge, UK

8Current address: Department of Pathology, University of Dammam, Dammam, KSA

*These authors have contributed equally to this work

Correspondence to:

Generoso Bevilacqua, e-mail: [email protected]

Keywords: Pathology Section, mouse mammary tumor virus (MMTV), breast cancer, breast cancer etiology, saliva

Received: April 12, 2015     Accepted: July 03, 2015     Published: July 15, 2015


Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma. Moreover, this experimental model contributed substantially to our understanding of many biological aspects of the human disease. Several data strongly suggest a causative role of MMTV in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral particles in primary cultures of breast cancer, the ability of the virus to infect cells in culture. This paper demonstrates that MMTV is present in human saliva and salivary glands. MMTV presence was investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole transcriptome analysis. Saliva was obtained from newborns, children, adults, and breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is present in saliva of children (26.66%), healthy adults (10.60%), and breast cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10% of salivary glands. RNA-seq analysis performed on saliva of a breast cancer patient demonstrates a high expression of MMTV RNA in comparison to negative controls. The possibility of a contamination by murine DNA was excluded by murine mtDNA and IAP LTR PCR. These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a viral origin for human breast carcinoma.

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