Abstract
Mouse mammary tumour virus-like (MMTV-like) is suspected to be involved in human breast cancer and it has been hypothesized that companion animals might have a role in viral transmission. The aim of our study was to investigate the presence of MMTV-like nucleotide sequences and viral protein in a larger number of feline (FMCs) and canine mammary carcinomas (CMCs) by nested PCR and immunohistochemistry. Results showed that the presence of MMTV-like env sequence in FMCs was 7% (6/86), while all the CMCs and canine dysplastic lesions scored negative. All PCR-positive FMCs scored positive for the MMTV p14 signal peptide of the envelope precursor protein of the virus. In contrast, all PCR-negative FMCs and canine mammary lesions were also negative for immunohistochemistry analysis. Canine and feline normal mammary gland tissues scored negative for both PCR and MMTV-p14 protein. Multiple nucleotide alignment of MMTV-like env gene sequences isolated from cat showed 97% and 99% similarity with HMTV and MMTV, respectively, while the others two presented some polimorphisms. Particularly the sequences of one of these two tumors showed a polymorphism (c.7575 A> G), that causes a previously unreported amino acid substitution (Thr > Ala). In conclusion, the results of our study showed the presence of MMTV-like sequences and viral protein in some FMCs. Further studies are needed to understand whether this virus does play a role in the development of FMCs, if MMTV-like is an exogenous virus as these data suggest and, in such a case, how and from whom this virus was acquired.
Highlights
The mouse mammary tumor virus (MMTV) is the prototype of slow-transforming retroviruses and is classified in the Betaretroviridae
Endogenous MMTV is frequently detected in laboratory mouse strains, but most of these endogenous viruses do not produce viral infectious particles due to transcriptional regulatory or coding region mutation [4]
Five-micrometer-thick-sections were stained with hematoxylin and eosin (HE) for histological evaluation; additional 5-μm sections were used for immunohistochemical studies
Summary
The mouse mammary tumor virus (MMTV) is the prototype of slow-transforming retroviruses and is classified in the Betaretroviridae. This virus is known to cause mammary carcinoma and lymphoma in susceptible mice [1, 2]. The involvement of a MMTV-like virus in human breast cancer has been proposed, based on the presence of MMTV-like sequences highly expresses in human breast cancer, and sharing over 95% identity with MMTV [5,6,7,8] This hypothesis is supported by the evidence that viral particles produced in primary cell cultures derived from human breast cancer are similar to those of MMTV [9]
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