Mouse Mammary Tumor Virus-Like Nucleotide Sequences in Canine and Feline Mammary Tumors

Abstract

Mouse mammary tumor virus (MMTV) has been speculated to be involved in human breast cancer. Companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of MMTV between mouse and human. The aim of this study was to detect MMTV-like nucleotide sequences in canine and feline mammary tumors by nested PCR. Results showed that the presence of MMTV-like env and LTR sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. For feline malignant mammary tumors, the presence of both env and LTR sequences was found to be 22.22% (2/9). Nevertheless, the MMTV-like LTR and env sequences also were detected in normal mammary glands of dogs and cats. In comparisons of the MMTV-like DNA sequences of our findings to those of NIH 3T3 (MMTVpositive murine cell line) and human breast cancer cells, the sequence similarities ranged from 94 to 98%. Phylogenetic analysis revealed that intermixing among sequences identified from tissues of different hosts, i.e., mouse, dog, cat, and human, indicated the MMTV-like DNA existing in these hosts. Moreover, the env transcript was detected in 1 of the 19 MMTV-positive samples by reverse transcription-PCR. Taken together, our study provides evidence for the existence and expression of MMTV-like sequences in neoplastic and normal mammary glands of dogs and cats.Several environmental risk factors have been proposed for sporadic human breast cancer, including mouse mammary tumor virus (MMTV). MMTV is an oncogenic retrovirus that induces breast cancer in mice and that can be isolated either as an endogenous or exogenous virus (3). Possible links of MMTV to human breast cancer have been indicated. Previous studies have demonstrated that MMTV-like sequences, which share at least 95% identity with MMTV, are highly expressed in human breast cancer (7,(28)(29)(30). Furthermore, viral particles produced in primary cell cultures derived from breast cancer are similar to those of MMTV (18).In addition, geographical variations in the incidence of human breast cancer with the distribution map of the natural range of certain species of mice, particularly Mus domesticus, were correlated. The area where M. domesticus mice are endemic coincides to a large extent with the countries having a high prevalence of breast cancer (22). A previous study reported that MMTV-positive samples were found only in the Australian group (with high incidences of breast cancer and M. domesticus) but not in the Vietnamese group (low prevalence of breast cancer and M. domesticus) (10). These results suggest that M. domesticus harbors and transfers a human-tropic strain of MMTV. However, the contribution of MMTV to breast carcinogenesis was not endorsed by recent studies, which reported no evidence for the existence of MMTV-like sequences in human breast cancer of Germanic (11) and Japanese patients (12). The controversial finding could be explained by the fact that Mus domesticus is not widely distributed in Germany (11) or Japan (12).Moreover, besides human and...

Familial incidence of mammary gland tumours in the Djungarian hamster (Phodopus sungaros): a case report

“…For the detection of endogenous Djungarian hamster provirus DNA (MRS-Ps) derived from mouse mammary tumour virus (MMTV) the DNA isolates were analysed by amplification of DNA fragments using the poly- Table 2. Amplification and sequencing primers for detection of endogenous MMTV DNA (Hsu et al 2010 GGA-TGG-CGA-ACA-GAC-ACA-AAC-AC Figure 7. Carcinoma in situ (blue arrows) and initial phase of invasion of carcinoma cells into adjacent connective tissue (red arrows); staining with HE merase chain reaction (PCR).…”

“…Carcinoma in situ (blue arrows) and initial phase of invasion of carcinoma cells into adjacent connective tissue (red arrows); staining with HE merase chain reaction (PCR). According to Hsu et al (2010) a primer set of eight specific amplification and sequencing primers for the detection of mouse mammary virus-like nucleotide sequences were used (Table 2). The PCR reactions were performed in a 50 µl amplification mix using the PPP master mix (TopBio, Prague) with different primer combinations.…”

Investigation of human papillomaviruses (HPV), mouse mammary tumour virus (MMTV), Epstein–Barr virus (EBV), and human polyomavirus entities in canine mammary tumours

“…Hsu et al (8) reported the presence of MMTV-like nucleotide sequences in canine and feline mammary tumours. They used the nested PCR method in CMT tissues and detected 3.49% of MMTV-like env and LTR sequences.…”

“…To the best of our knowledge, only Hsu et al (8) have investigated MMTV-like sequences in canine and feline mammary tumours and normal mammary tissues (not in cell lines), but EBV, HPV, and PV have never been investigated as aetiological factors. Thus, the aim of this study was to evaluate the possible pathogenic properties of these viruses in dog mammary tumours.…”

Tumorigenesis related to retroviral infections

“…Previous reports suggested the involvement of MMTV in neoplastic mammary glands of cats and dogs. Companion animals might contribute to the transmission of MMTV between mouse and man [51]. MMTV-like virus DNA has been detected in several human cancers including breast, liver, ovarian, prostate, endometrial, and skin malignancies [52,53].…”