title: Human saliva as route of inter-human infection for mouse mammary tumor virus.
abstract: 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.
authors.affiliation: FPS - The Pisa Science Foundation, Pisa, Italy.
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Mazzanti
authors.affiliation: FPS - The Pisa Science Foundation, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lessi
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.|Presently at Illumina Cambridge Ltd, Cambridge, UK.
authors.forename: Ivana
authors.initials: I
authors.lastname: Armogida
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Zavaglia
authors.affiliation: FPS - The Pisa Science Foundation, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Franceschi
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.|Presently at the Department of Pathology, University of Dammam, Dammam, KSA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al Hamad
authors.affiliation: Breast Center, Department of Breast Surgery, Pisa University Hospital, Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Roncella
authors.affiliation: Breast Center, Department of Breast Surgery, Pisa University Hospital, Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ghilli
authors.affiliation: Department of Neonatology, Pisa University Hospital, Pisa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Boldrini
authors.affiliation: FPS - The Pisa Science Foundation, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Aretini
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fanelli
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.
authors.forename: Ivo
authors.initials: I
authors.lastname: Marchetti
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Scatena
authors.affiliation: Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hochman
authors.affiliation: Department of Pathology, Pisa University Hospital, Pisa, Italy.|Laboratory of Pathology, "San Rossore" Hospital, Pisa, Italy.
authors.forename: Antonio Giuseppe
authors.initials: AG
authors.lastname: Naccarato
authors.affiliation: FPS - The Pisa Science Foundation, Pisa, Italy.|Department of Pathology, Pisa University Hospital, Pisa, Italy.
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000821:virology; D005260:Female; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008875:Middle Aged; D012192:Retroviridae Infections / Q000635:transmission / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000821:virology*; D012469:Salivary Glands / Q000821:virology; D014412:Tumor Virus Infections / Q000635:transmission / Q000821:virology*
keywords: Pathology Section; breast cancer; breast cancer etiology; mouse mammary tumor virus (MMTV); saliva