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Oncotarget. 2015 Jul 30;6(21):18355-63.

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

Author information

FPS - The Pisa Science Foundation, Pisa, Italy.
Department of Pathology, Pisa University Hospital, Pisa, Italy.
Presently at Illumina Cambridge Ltd, Cambridge, UK.
Presently at the Department of Pathology, University of Dammam, Dammam, KSA.
Breast Center, Department of Breast Surgery, Pisa University Hospital, Pisa, Italy.
Department of Neonatology, Pisa University Hospital, Pisa, Italy.
Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Laboratory of Pathology, "San Rossore" Hospital, Pisa, Italy.


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.


Pathology Section; breast cancer; breast cancer etiology; mouse mammary tumor virus (MMTV); saliva

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